bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotyping of Coxiella burnetiifrom domestic ruminants in northern Spain
Authors: Astobiza Ianire , Tilburg Jeroen JHC , Piñero Alvaro , Hurtado Ana , García-Pérez Ana L , Nabuurs-Franssen Marrigje H , Klaassen Corné HW 
Published: December 2012

AbstractBackgroundInformation on the genotypic diversity ofCoxiella burnetiiisolates from infected domestic ruminants in Spain is limited. The aim of this study was to identify theC. burnetiigenotypes infecting livestock in Northern Spain and compare them to other European genotypes. A commercial real-time PCR targeting the IS1111ainsertion element was used to detect the presence ofC. burnetiiDNA in domestic ruminants from Spain. Genotypes were determined by a 6-loci Multiple Locus Variable number tandem repeat analysis (MLVA) panel and Multispacer Sequence Typing (MST).ResultsA total of 45 samples from 4 goat herds (placentas, N = 4), 12 dairy cattle herds (vaginal mucus, individual milk, bulk tank milk, aerosols, N = 20) and 5 sheep flocks (placenta, vaginal swabs, faeces, air samples, dust, N = 21) were included in the study. Samples from goats and sheep were obtained from herds which had suffered abortions suspected to be caused byC. burnetii, whereas cattle samples were obtained from animals with reproductive problems compatible withC. burnetiiinfection, or consisted of bulk tank milk (BTM) samples from a Q fever surveillance programme.C. burnetiigenotypes identified in ruminants from Spain were compared to those detected in other countries. Three MLVA genotypes were found in 4 goat farms, 7 MLVA genotypes were identified in 12 cattle herds and 4 MLVA genotypes were identified in 5 sheep flocks. Clustering of the MLVA genotypes using the minimum spanning tree method showed a high degree of genetic similarity between most MLVA genotypes. Overall 11 different MLVA genotypes were obtained corresponding to 4 different MST genotypes: MST genotype 13, identified in goat, sheep and cattle from Spain; MST genotype 18, only identified in goats; and, MST genotypes 8 and 20, identified in small ruminants and cattle, respectively. All these genotypes had been previously identified in animal and human clinical samples from several European countries, but some of the MLVA genotypes are described here for the first time.ConclusionsGenotyping revealed a substantial genetic diversity among domestic ruminants from Northern Spain.
Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach
Authors: Fan Shengjun , Geng Qiang , Pan Zhenyu , Li Xin , Tie Lu , Pan Yan , Li Xuejun 
Published: December 2012

Abstract

Background
Torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor which raises high-density lipoprotein (HDL) cholesterol and reduces low-density lipoprotein (LDL) cholesterol level, has been documented to increase mortality and cardiac events associated with adverse effects. However, it is still unclear the underlying mechanisms of the off-target effects of torcetrapib.

Results
In the present study, we developed a systems biology approach by combining a human reassembled signaling network with the publicly available microarray gene expression data to provide unique insights into the off-target adverse effects for torcetrapib. Cytoscape with three plugins including BisoGenet, NetworkAnalyzer and ClusterONE was utilized to establish a context-specific drug-gene interaction network. The DAVID functional annotation tool was applied for gene ontology (GO) analysis, while pathway enrichment analysis was clustered by ToppFun. Furthermore, potential off-targets of torcetrapib were predicted by a reverse docking approach. In general, 10503 nodes were retrieved from the integrative signaling network and 47660 inter-connected relations were obtained from the BisoGenet plugin. In addition, 388 significantly up-regulated genes were detected by Significance Analysis of Microarray (SAM) in adrenal carcinoma cells treated with torcetrapib. After constructing the human signaling network, the over-expressed microarray genes were mapped to illustrate the context-specific network. Subsequently, three conspicuous gene regulatory networks (GRNs) modules were unearthed, which contributed to the off-target effects of torcetrapib. GO analysis reflected dramatically over-represented biological processes associated with torcetrapib including activation of cell death, apoptosis and regulation of RNA metabolic process. Enriched signaling pathways uncovered that IL-2 Receptor Beta Chain in T cell Activation, Platelet-Derived Growth Factor Receptor (PDGFR) beta signaling pathway, IL2-mediated signaling events, ErbB signaling pathway and signaling events mediated by Hepatocyte Growth Factor Receptor (HGFR, c-Met) might play decisive characters in the adverse cardiovascular effects associated with torcetrapib. Finally, a reverse docking algorithm in silico between torcetrapib and transmembrane receptors was conducted to identify the potential off-targets. This screening was carried out based on the enriched signaling network analysis.

Conclusions
Our study provided unique insights into the biological processes of torcetrapib-associated off-target adverse effects in a systems biology visual angle. In particular, we highlighted the importance of PDGFR, HGFR, IL-2 Receptor and ErbB1tyrosine kinase might be direct off-targets, which were highly related to the unfavorable adverse effects of torcetrapib and worthy of further experimental validation.
The effect of Cinnamaldehyde on mucositis and salivary antioxidant capacity in gamma-irradiated rats (a preliminary study)
Authors: Molania Tahereh , Moghadamnia Ali Akbar , Pouramir Mahdi , Aghel Sara , Moslemi Dariush , Ghassemi Leila , Motallebnejad Mina 
Published: December 2012

Abstract

Background and purpose of the study
The aim of this study was to investigate the effect of cinnamaldehyde on mucositis and salivary total antioxidant capacity in gamma-irradiated rats.

Methods
The study was conducted on 28 male Wistar rats, 7–11 weeks of age and 160 ± 20 g body weight, divided into four groups of seven rats each. The first group receiving normal saline (S), the second group receiving saline and gamma radiation (SR), the third group receiving 50 mg/kg cinnamaldehyde 98% (C), and the fourth group receiving 50 mg/kg cinnamaldehyde 98% and gamma radiation (CR). SR and CR groups were exposed to 15 Gy gamma irradiation for 7 min and 39 s. Rats were intraperitoneally injected each day during the 10-day period of the experiment, and their tongues and lips were examined to assess the incidence and severity of mucositis. The saliva samples were taken from the animals three times on day zero, six, and ten.

Results
The mean mucositis incidence appeared to be delayed in the CR than the SR group (P = 0.024), and the severity was significantly higher in the SR compared to the CR group;the difference was statistically significant on the second day (P = 0.027). In the evaluation of salivary antioxidant capacity, salivary antioxidant concentration was significantly higher in the C than the S, SR, and CR groups on the tenth day of the experiment (p <0.05).

Conclusion
The clinical effects in the CR group seem to be due to antioxidant, anti-bacterial and anti-inflammatory effects of cinnamaldehyde; this conclusion, however, requires further investigations. Delayed antioxidant effect in the CR group was evident in ip cinnamaldehyde injection, the exact mechanism is not clear.
COX-2 structural analysis and docking studies with gallic acid structural analogues
Authors: Amaravani M , Prasad Nirmal K , Ramakrishna Vadde 
Published: December 2012

Abstract

Emblica officinalis is an ayurvedic herbal plant. The compounds isolated from this plant have good inhibitory effects against cyclooxygenase-2 (COX-2), among them gallic acid (GA) has the highest inhibitory effect. COX-2 (1.14.99.1)is an oxidoreductase having a role in prostaglandin biosynthesis, inflammatory responses and in cardiovascular events. COX-2 has gained special focus on research since past few decades. The sequence and structural studies reveals Mus musculus COX-2 shares the common conserved sequence and structural pattern with human COX-2. Molecular modeling and docking analysis with gallic acid and their structural analogues showed that 2-[(2E,4E)-hexa-2,4-dienyl]-3,4,5-trihydroxybenzoic acid, (3,4,5-trihydroxybenzoyl) 3,4,5-trihydroxybenzoate and 3-hydroxy-4-sulfooxybenzoic acid are more interactive and binding strongly than gallic acid at active site. Hence these three compounds should be considered as strong inhibitors for COX-2.
Iridium(III) products isolated in a reaction of IrCl3 with phenyl 2-pyridyl ketoxime
Authors: Hołyńska Małgorzata 
Published: December 2012

Abstract
Synthesis and properties of two iridium(III) complexes (1 and 2) isolated from the same system upon change in organic solvent, are presented. 1 is a mononuclear compound with two bidentate oxime ligands linked by a strong intramolecular hydrogen bond and with two chlorido ligands in the central Ir3+ ion coordination sphere. 2 is a binuclear centrosymmetric anionic complex with two Ir3+ ions double-bridged by chlorido ligands and three terminal chlorido ligands further coordinated to two sodium cations to form a characteristic aggregate with acetonitrile molecules completing coordination spheres of the metal ions. Both 1 and 2 may help to develop a route to products analogous to Co(II) SMMs (Single Molecule Magnets) also as starting materials.
Mapping Six New Susceptibility to Colon Cancer (Scc) Loci Using a Mouse Interspecific Backcross
Authors: Eversley Chevonne D , Yuying Xie , Pearsall R Scott , Threadgill David W 
Published: December 2012

AbstractColorectal cancer (CRC) has a complex etiology resulting from the combination of multiple genetic and environmental factors, each with small effects. Interactions among susceptibility modifier loci make many of the loci difficult to detect in human genome-wide association studies. Previous analyses in mice have used classical inbred strains, which share large portions of their genomes due to common ancestry. Herein, we used an interspecific backcross between the Mus musculus strain A/J and the Mus spretus strain SPRET/EiJ to map 6 additional CRC modifier loci (Scc16-21) and 2 suggestive loci. Three loci modify the location of tumors along the proximal-distal axis of the colon. Six CRC modifiers previously mapped in intraspecific crosses were also replicated. This work confirms genetic models suggesting that CRC is caused by many small effect alleles and brings the catalog of reported CRC modifier loci to 23 spread across 13 chromosomes. Furthermore, this work provides the foundation for large population-level epistatic interaction tests to identify combinations of low effect alleles that may have large effects on CRC susceptibility.
Suppressors ofipl1-2in Components of a Glc7 Phosphatase Complex, Cdc48 AAA ATPase, TORC1, and the Kinetochore
Authors: Robinson Lucy C , Phillips Joshua , Brou Lina , Boswell Evan P , Tatchell Kelly 
Published: December 2012

AbstractIpl1/Aurora B is the catalytic subunit of a protein kinase complex required for chromosome segregation and nuclear division. Before anaphase, Ipl1 is required to establish proper kinetochore-microtubule associations and to regulate the spindle assembly checkpoint (SAC). The phosphatase Glc7/PP1 opposes Ipl1 for these activities. To investigate Ipl1 and Glc7 regulation in more detail, we isolated and characterized mutations in the yeast Saccharomyces cerevisiae that raise the restrictive temperature of the ipl-2 mutant. These suppressors include three intragenic, second-site revertants in IPL1; 17 mutations in Glc7 phosphatase components (GLC7, SDS22, YPI1); two mutations in SHP1, encoding a regulator of the AAA ATPase Cdc48; and a mutation in TCO89, encoding a subunit of the TOR Complex 1. Two revertants contain missense mutations in microtubule binding components of the kinetochore. rev76 contains the missense mutation duo1-S115F, which alters an essential component of the DAM1/DASH complex. The mutant is cold sensitive and arrests in G2/M due to activation of the SAC. rev8 contains the missense mutation ndc80-K204E. K204 of Ndc80 corresponds to K166 of human Ndc80 and the human Ndc80 K166E variant was previously shown to be defective for microtubule binding in vitro. In a wild-type IPL1 background, ndc80-K204E cells grow slowly and the SAC is activated. The slow growth and cell cycle delay of ndc80-K204E cells are partially alleviated by the ipl1-2 mutation. These data provide biological confirmation of a biochemically based model for the effect of phosphorylation on Ndc80 function.
Iron Deprivation inSynechocystis: Inference of Pathways, Non-coding RNAs, and Regulatory Elements from Comprehensive Expression Profiling
Authors: Hernández-Prieto Miguel A , Schön Verena , Georg Jens , Barreira Luísa , Varela João , Hess Wolfgang R , Futschik Matthias E 
Published: December 2012

AbstractIron is an essential cofactor in many metabolic reactions. Mechanisms controlling iron homeostasis need to respond rapidly to changes in extracellular conditions, but they must also keep the concentration of intracellular iron under strict control to avoid the generation of damaging reactive oxygen species. Due to its role as a redox carrier in photosynthesis, the iron quota in cyanobacteria is about 10 times higher than in model enterobacteria. The molecular details of how such a high quota is regulated are obscure. Here we present experiments that shed light on the iron regulatory system in cyanobacteria. We measured time-resolved changes in gene expression after iron depletion in the cyanobacterium Synechocystis sp. PCC 6803 using a comprehensive microarray platform, monitoring both protein-coding and non-coding transcripts. In total, less than a fifth of all protein-coding genes were differentially expressed during the first 72 hr. Many of these proteins are associated with iron transport, photosynthesis, or ATP synthesis. Comparing our data with three previous studies, we identified a core set of 28 genes involved in iron stress response. Among them were genes important for assimilation of inorganic carbon, suggesting a link between the carbon and iron regulatory networks. Nine of the 28 genes have unknown functions and constitute key targets for further functional analysis. Statistical and clustering analyses identified 10 small RNAs, 62 antisense RNAs, four 5′UTRs, and seven intragenic elements as potential novel components of the iron regulatory network in Synechocystis. Hence, our genome-wide expression profiling indicates an unprecedented complexity in the iron regulatory network of cyanobacteria.
Invariance (?) of Mutational Parameters for Relative Fitness Over 400 Generations of Mutation Accumulation inCaenorhabditis elegans
Authors: Matsuba Chikako , Lewis Suzanna , Ostrow Dejerianne G , Salomon Matthew P , Sylvestre Laurence , Tabman Brandon , Ungvari-Martin Judit , Baer Charles F 
Published: December 2012

AbstractEvidence is accumulating that individuals in poor physiologic condition may accumulate mutational damage faster than individuals in good condition. If poor condition results from pre-existing deleterious mutations, the result is “fitness-dependent mutation rate,” which has interesting theoretical implications. Here we report a study in which 10 mutation accumulation (MA) lines of the nematode Caenorhabditis elegans that had previously accumulated mutations for 250 generations under relaxed selection were expanded into sets of “second-order” MA lines and allowed to accumulate mutations for an additional 150 generations. The 10 lines were chosen on the basis of the relative change in fitness over the first 250 generations of MA, five high-fitness lines and five low-fitness lines. On average, the mutational properties (per-generation change in mean relative fitness, mutational variance, and Bateman-Mukai estimates of genomic mutation rate and average mutational effect) of the high-fitness and low-fitness did not differ significantly, and averaged over all lines, the point estimates were extremely close to those of the first-order MA experiment after 200 generations of MA. However, several nonsignificant trends indicate that low-fitness lines may in fact be more likely to suffer mutational damage than high-fitness lines.
Genetic Control of Vulval Development inCaenorhabditis briggsae
Authors: Sharanya Devika , Thillainathan Bavithra , Marri Sujatha , Bojanala Nagagireesh , Taylor Jon , Flibotte Stephane , Moerman Donald G , Waterston Robert H , Gupta Bhagwati P 
Published: December 2012

AbstractThe nematode Caenorhabditis briggsae is an excellent model organism for the comparative analysis of gene function and developmental mechanisms. To study the evolutionary conservation and divergence of genetic pathways mediating vulva formation, we screened for mutations in C. briggsae that cause the egg-laying defective (Egl) phenotype. Here, we report the characterization of 13 genes, including three that are orthologs of Caenorhabditis elegans unc-84 (SUN domain), lin-39 (Dfd/Scr-related homeobox), and lin-11 (LIM homeobox). Based on the morphology and cell fate changes, the mutants were placed into four different categories. Class 1 animals have normal-looking vulva and vulva-uterine connections, indicating defects in other components of the egg-laying system. Class 2 animals frequently lack some or all of the vulval precursor cells (VPCs) due to defects in the migration of P-cell nuclei into the ventral hypodermal region. Class 3 animals show inappropriate fusion of VPCs to the hypodermal syncytium, leading to a reduced number of vulval progeny. Finally, class 4 animals exhibit abnormal vulval invagination and morphology. Interestingly, we did not find mutations that affect VPC induction and fates. Our work is the first study involving the characterization of genes in C. briggsae vulva formation, and it offers a basis for future investigations of these genes in C. elegans.
Genetic Analysis of Mps3 SUN Domain Mutants inSaccharomyces cerevisiaeReveals an Interaction with the SUN-Like Protein Slp1
Authors: Friederichs Jennifer M , Gardner Jennifer M , Smoyer Christine J , Whetstine Christine R , Gogol Madelaine , Slaughter Brian D , Jaspersen Sue L 
Published: December 2012

AbstractIn virtually all eukaryotic cells, protein bridges formed by the conserved inner nuclear membrane SUN (for Sad1-UNC-84) domain-containing proteins and their outer nuclear membrane binding partners span the nuclear envelope (NE) to connect the nucleoplasm and cytoplasm. These linkages are important for chromosome movements within the nucleus during meiotic prophase and are essential for nuclear migration and centrosome attachment to the NE. In Saccharomyces cerevisiae, MPS3 encodes the sole SUN protein. Deletion of MPS3 or the conserved SUN domain is lethal in three different genetic backgrounds. Mutations in the SUN domain result in defects in duplication of the spindle pole body, the yeast centrosome-equivalent organelle. A genome-wide screen for mutants that exhibited synthetic fitness defects in combination with mps3 SUN domain mutants yielded a large number of hits in components of the spindle apparatus and the spindle checkpoint. Mutants in lipid metabolic processes and membrane organization also exacerbated the growth defects of mps3 SUN domain mutants, pointing to a role for Mps3 in nuclear membrane organization. Deletion of SLP1 or YER140W/EMP65 (for ER membrane protein of 65 kDa) aggravated growth of mps3 SUN domain mutants. Slp1 and Emp65 form an ER-membrane associated protein complex that is not required directly for spindle pole body duplication or spindle assembly. Rather, Slp1 is involved in Mps3 localization to the NE.
The Impact of Sand and Asphaltic Production Problems on Pressure Behavior and Flow Regimes
Authors: Al Rbeawi Salam , Tiab D.. 
Published: December 2012

Abstract
Asphaltic and sand production problems are common production challenges in the petroleum industry. Asphaltic problem results from the depositions of heavy material (asphaltene) in the vicinity of the well which may cause severe formation damage. Asphaltic materials are expected to deposit in all type of reservoirs. Sand production refers to the phenomenon of solid particles being produced together with the petroleum fluids. These two problems represent a major concern in oil and gas production systems either in the wellbore section or in the surface treatment facilities. Production data, well logging, laboratory testing, acoustic, intrusive sand monitoring devices, and analogy are different techniques used to predict sand production. This paper introduces a new technique to predict and quantify the skin factor resulting from asphaltene deposition and/or sand production using pressure transient analysis.
Pressure behavior and flow regimes in the vicinity of horizontal wellbore are extremely influenced by this skin factor. Analytical models for predicting this problem and determining how many zones of the horizontal well that are affected by sand production or asphaltic deposition have been introduced in this study. These models have been derived based on the assumption that wellbore can be divided into multi-subsequent segments of producing and non-producing intervals. Producing intervals represent free flowing zones while non producing intervals represent zones where perforations are closed because of sand or asphaltic deposits.
The effective length of the segments of a horizontal well where sand and/or asphaltene are significantly closing the perforations can be calculated either from the early radial or linear flow. Similarly, the effective length of the undamaged segments can be determined from these two flow regimes. The numbers of the damaged and undamaged zones can be calculated either from the intermediate radial (secondary radial) or linear flow if they are observed. If both flow regimes are not observed, the zones can be calculated using type curve matching technique. The paper will include the main type-curves, step-by-step procedure for interpreting the pressure test without using type curve matching technique when all necessary flow regimes are observed. A step-by-step procedure for analyzing pressure tests using the type-curve matching technique will also be presented. The procedure will be illustrated by several numerical examples.