bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron-deficiency anemia from matriptase-2 inactivation is dependent on the presence of functional Bmp6
Authors: Lenoir Anne , Deschemin Jean-Christophe , Kautz Léon , Ramsay Andrew J. , Roth Marie-Paule , Lopez-Otin Carlos , Vaulont Sophie , Nicolas Gaël 
Published: October 2010

Abstract
Hepcidin is the master regulator of iron homeostasis. In the liver, iron-dependent hepcidin activation is regulated through Bmp6 and its membrane receptor hemojuvelin (Hjv), whereas, in response to iron deficiency, hepcidin repression seems to be controlled by a pathway involving the serine protease matriptase-2 (encoded by Tmprss6). To determine the relationship between Bmp6 and matriptase-2 pathways, Tmprss6−/− mice (characterized by increased hepcidin levels and anemia) and Bmp6−/− mice (exhibiting severe iron overload because of hepcidin deficiency) were intercrossed. We showed that loss of Bmp6 decreased hepcidin levels; increased hepatic iron; and, importantly, corrected hematologic abnormalities in Tmprss6−/− mice. This finding suggests that elevated hepcidin levels in patients with familial iron-refractory, iron-deficiency anemia are the result of excess signaling through the Bmp6/Hjv pathway.
Trimming of mammalian transcriptional networks using network component analysis
Authors: Tran Linh M , Hyduke Daniel R , Liao James C 
Published: October 2010

AbstractBackgroundNetwork Component Analysis (NCA) has been used to deduce the activities of transcription factors (TFs) from gene expression data and the TF-gene binding relationship. However, the TF-gene interaction varies in different environmental conditions and tissues, but such information is rarely available and cannot be predicted simply by motif analysis. Thus, it is beneficial to identify key TF-gene interactions under the experimental condition based on transcriptome data. Such information would be useful in identifying key regulatory pathways and gene markers of TFs in further studies.ResultsWe developed an algorithm to trim network connectivity such that the important regulatory interactions between the TFs and the genes were retained and the regulatory signals were deduced. Theoretical studies demonstrated that the regulatory signals were accurately reconstructed even in the case where only three independent transcriptome datasets were available. At least 80% of the main target genes were correctly predicted in the extreme condition of high noise level and small number of datasets. Our algorithm was tested with transcriptome data taken from mice under rapamycin treatment. The initial network topology from the literature contains 70 TFs, 778 genes, and 1423 edges between the TFs and genes. Our method retained 1074 edges (i.e. 75% of the original edge number) and identified 17 TFs as being significantly perturbed under the experimental condition. Twelve of these TFs are involved in MAPK signaling or myeloid leukemia pathways defined in the KEGG database, or are known to physically interact with each other. Additionally, four of these TFs, which are Hif1a, Cebpb, Nfkb1, and Atf1, are known targets of rapamycin. Furthermore, the trimmed network was able to predictEno1as an important target of Hif1a; this key interaction could not be detected without trimming the regulatory network.ConclusionsThe advantage of our new algorithm, relative to the original NCA, is that our algorithm can identify the important TF-gene interactions. Identifying the important TF-gene interactions is crucial for understanding the roles of pleiotropic global regulators, such as p53. Also, our algorithm has been developed to overcome NCA's inability to analyze large networks where multiple TFs regulate a single gene. Thus, our algorithm extends the applicability of NCA to the realm of mammalian regulatory network analysis.
Evolutionary history of the poly(ADP-ribose) polymerase gene family in eukaryotes
Authors: Citarelli Matteo , Teotia Sachin , Lamb Rebecca S 
Published: October 2010

Abstract

Background
The Poly(ADP-ribose)polymerase (PARP) superfamily was originally identified as enzymes that catalyze the attachment of ADP-ribose subunits to target proteins using NAD+ as a substrate. The family is characterized by the catalytic site, termed the PARP signature. While these proteins can be found in a range of eukaryotes, they have been best studied in mammals. In these organisms, PARPs have key functions in DNA repair, genome integrity and epigenetic regulation. More recently it has been found that proteins within the PARP superfamily have altered catalytic sites, and have mono(ADP-ribose) transferase (mART) activity or are enzymatically inactive. These findings suggest that the PARP signature has a broader range of functions that initially predicted. In this study, we investigate the evolutionary history of PARP genes across the eukaryotes.

Results
We identified in silico 236 PARP proteins from 77 species across five of the six eukaryotic supergroups. We performed extensive phylogenetic analyses of the identified PARPs. They are found in all eukaryotic supergroups for which sequence is available, but some individual lineages within supergroups have independently lost these genes. The PARP superfamily can be subdivided into six clades. Two of these clades were likely found in the last common eukaryotic ancestor. In addition, we have identified PARPs in organisms in which they have not previously been described.

Conclusions
Three main conclusions can be drawn from our study. First, the broad distribution and pattern of representation of PARP genes indicates that the ancestor of all extant eukaryotes encoded proteins of this type. Second, the ancestral PARP proteins had different functions and activities. One of these proteins was similar to human PARP1 and likely functioned in DNA damage response. The second of the ancestral PARPs had already evolved differences in its catalytic domain that suggest that these proteins may not have possessed poly(ADP-ribosyl)ation activity. Third, the diversity of the PARP superfamily is larger than previously documented, suggesting as more eukaryotic genomes become available, this gene family will grow in both number and type.
Variance heterogeneity analysis for detection of potentially interacting genetic loci: method and its limitations
Authors: Struchalin Maksim V , Dehghan Abbas , Witteman Jacqueline CM , van Duijn Cornelia , Aulchenko Yurii S 
Published: October 2010

Abstract

Background
Presence of interaction between a genotype and certain factor in determination of a trait's value, it is expected that the trait's variance is increased in the group of subjects having this genotype. Thus, test of heterogeneity of variances can be used as a test to screen for potentially interacting single-nucleotide polymorphisms (SNPs). In this work, we evaluated statistical properties of variance heterogeneity analysis in respect to the detection of potentially interacting SNPs in a case when an interaction variable is unknown.

Results
Through simulations, we investigated type I error for Bartlett's test, Bartlett's test with prior rank transformation of a trait to normality, and Levene's test for different genetic models. Additionally, we derived an analytical expression for power estimation. We showed that Bartlett's test has acceptable type I error in the case of trait following a normal distribution, whereas Levene's test kept nominal Type I error under all scenarios investigated. For the power of variance homogeneity test, we showed (as opposed to the power of direct test which uses information about known interacting factor) that, given the same interaction effect, the power can vary widely depending on the non-estimable direct effect of the unobserved interacting variable. Thus, for a given interaction effect, only very wide limits of power of the variance homogeneity test can be estimated. Also we applied Levene's approach to test genome-wide homogeneity of variances of the C-reactive protein in the Rotterdam Study population (n = 5959). In this analysis, we replicate previous results of Pare and colleagues (2010) for the SNP rs12753193 (n = 21, 799).

Conclusions
Screening for differences in variances among genotypes of a SNP is a promising approach as a number of biologically interesting models may lead to the heterogeneity of variances. However, it should be kept in mind that the absence of variance heterogeneity for a SNP can not be interpreted as the absence of involvement of the SNP in the interaction network.
Characterization of the rainbow trout transcriptome using Sanger and 454-pyrosequencing approaches
Authors: Salem Mohamed , Rexroad Caird E , Wang Jiannan , Thorgaard Gary H , Yao Jianbo 
Published: October 2010

Abstract

Background
Rainbow trout are important fish for aquaculture and recreational fisheries and serves as a model species for research investigations associated with carcinogenesis, comparative immunology, toxicology and evolutionary biology. However, to date there is no genome reference sequence to facilitate the development of molecular technologies that utilize high-throughput characterizations of gene expression and genetic variation. Alternatively, transcriptome sequencing is a rapid and efficient means for gene discovery and genetic marker development. Although a large number (258,973) of EST sequences are publicly available, the nature of rainbow trout duplicated genome hinders assembly and complicates annotation.

Results
High-throughput deep sequencing of the Swanson rainbow trout doubled-haploid transcriptome using 454-pyrosequencing technology yielded ~1.3 million reads with an average length of 344 bp, a total of 447 million bases. De novo assembly of the sequences yielded 151,847 Tentative Consensus (TC) sequences (average length of 662 bp) and 224,391 singletons. A combination assembly of both the 454-pyrosequencing ESTs and the pre-existing sequences resulted in 161,818 TCs (average length of 758 bp) and 261,071 singletons. Gene Ontology analysis of the combination assembly showed high similarities to transcriptomes of other fish species with known genome sequences.

Conclusion
The 454 library significantly increased the suite of ESTs available for rainbow trout, allowing improved assembly and annotation of the transcriptome. Furthermore, the 454 sequencing enables functional genome research in rainbow trout, providing a wealth of sequence data to serve as a reference transcriptome for future studies including identification of paralogous sequences and/or allelic variation, digital gene expression and proteomic research.
Lack of association of the CIITA-168A→G promoter SNP with myasthenia gravis and its role in autoimmunity
Authors: Ramanujam Ryan , Zhao Yaofeng , Pirskanen Ritva , Hammarström Lennart 
Published: October 2010

Abstract

Background
The major histocompatibility complex class II transactivator (CIITA) regulates MHC class II gene expression. A promoter SNP -168A→G (rs3087456) has previously been shown to be associated with susceptibility to several immune mediated disorders, including rheumatoid arthritis (RA), multiple sclerosis (MS) and myocardial infarction (MI). Myasthenia gravis (MG) is an autoimmune disorder which has previously been shown to be associated with polymorphisms of several autoimmune predisposing genes, including IL-1, PTPN22, TNF-α and the MHC. In order to determine if allelic variants of rs3087456 increase predisposition to MG, we analyzed this SNP in our Swedish cohort of 446 MG patients and 1866 controls.

Results
No significant association of the SNP with MG was detected, neither in the patient group as a whole, nor in any clinical subgroup. The vast majority of previous replication studies have also not found an association of the SNP with autoimmune disorders.

Conclusions
We thus conclude that previous findings with regard to the role of the CIITA -168A→G SNP in autoimmunity may have to be reconsidered.
N-terminal and C-terminal heparin-binding domain polypeptides derived from fibronectin reduce adhesion and invasion of liver cancer cells
Authors: Tang Nan-Hong , Chen Yan-Lin , Wang Xiao-Qian , Li Xiu-Jin , Wu Yong , Zou Qi-Lian , Chen Yuan-Zhong 
Published: October 2010

AbstractBackgroundFibronectin (FN) is known to be a large multifunction glycoprotein with binding sites for many substances, including N-terminal and C-terminal heparin-binding domains. We investigated the effects of highly purified rhFNHN29 and rhFNHC36 polypeptides originally cloned from the two heparin-binding domains on the adhesion and invasion of highly metastatic human hepatocellular carcinoma cells (MHCC97H) and analyzed the underlying mechanism involved.MethodsThe MHCC97H cells that adhered to FN in the presence of various concentrations of rhFNHN29 and rhFNHC36 polypeptides were stained with crystal violet and measured, and the effects of rhFNHN29 and rhFNHC36 on the invasion of the MHCC97H cells were then detected using the Matrigel invasion assay as well as a lung-metastasis mouse model. The expression level of integrins and focal adhesion kinase (FAK) phosphotyrosyl protein was examined by Western blot, and the activity of matrix metalloproteinases (MMPs) and activator protein 1 (AP-1) was analyzed by gelatin zymography and the electrophoretic mobility band-shift assay (EMSA), respectively.ResultsBoth of the polypeptides rhFNHN29 and rhFNHC36 inhibited adhesion and invasion of MHCC97H cells; however, rhFNHC36 exhibited inhibition at a lower dose than rhFNHN29. These inhibitory effects were mediated by integrin αvβ3 and reversed by a protein tyrosine phosphatase inhibitor. Polypeptides rhFNHN29 and rhFNHC36 abrogated the tyrosine phosphorylation of focal adhesion kinase (p-FAK) and activation of activator protein 1 (AP-1), resulting in the decrease of integrin αv, β3 and β1 expression as well as the reduction of MMP-9 activity.ConclusionsPolypeptides rhFNHN29 and rhFNHC36 could potentially be applicable to human liver cancer as anti-adhesive and anti-invasive agents.
Expression pattern of matrix metalloproteinases in human gynecological cancer cell lines
Authors: Schröpfer Andrea , Kammerer Ulrike , Kapp Michaela , Dietl Johannes , Feix Sonja , Anacker Jelena 
Published: October 2010

Abstract

Background
Matrix metalloproteinases (MMPs) are involved in the degradation of protein components of the extracellular matrix and thus play an important role in tumor invasion and metastasis. Their expression is related to the progression of gynecological cancers (e.g. endometrial, cervical or ovarian carcinoma). In this study we investigated the expression pattern of the 23 MMPs, currently known in humans, in different gynecological cancer cell lines.

Methods
In total, cell lines from three endometrium carcinomas (Ishikawa, HEC-1-A, AN3 CA), three cervical carcinomas (HeLa, Caski, SiHa), three chorioncarcinomas (JEG, JAR, BeWo), two ovarian cancers (BG-1, OAW-42) and one teratocarcinoma (PA-1) were examined. The expression of MMPs was analyzed by RT-PCR, Western blot and gelatin zymography.

Results
We demonstrated that the cell lines examined can constitutively express a wide variety of MMPs on mRNA and protein level. While MMP-2, -11, -14 and -24 were widely expressed, no expression was seen for MMP-12, -16, -20, -25, -26, -27 in any of the cell lines. A broad range of 16 MMPs could be found in the PA1 cells and thus this cell line could be used as a positive control for general MMP experiments. While the three cervical cancer cell lines expressed 10-14 different MMPs, the median expression in endometrial and choriocarcinoma cells was 7 different enzymes. The two investigated ovarian cancer cell lines showed a distinctive difference in the number of expressed MMPs (2 vs. 10).

Conclusions
Ishikawa, Caski, OAW-42 and BeWo cell lines could be the best choice for all future experiments on MMP regulation and their role in endometrial, cervical, ovarian or choriocarcinoma development, whereas the teratocarcinoma cell line PA1 could be used as a positive control for general MMP experiments.
Predictors of switching antipsychotic medications in the treatment of schizophrenia
Authors: Nyhuis Allen W , Faries Douglas E , Ascher-Svanum Haya , Stauffer Virginia L , Kinon Bruce J 
Published: October 2010

Abstract

Background
To identify patient characteristics and early changes in patients' clinical status that best predict subsequent switching of antipsychotic agents in the long-term treatment of schizophrenia.

Methods
This post-hoc analysis used data from a one-year randomized, open-label, multisite study of antipsychotics in the treatment of schizophrenia. The study protocol permitted switching of antipsychotics when clinically warranted after the first eight weeks. Baseline patient characteristics were assessed using standard psychiatric measures and reviews of medical records. The prediction model included baseline sociodemographics, comorbid psychiatric and non-psychiatric conditions, body weight, clinical and functional variables, as well as change scores on standard efficacy and tolerability measures during the first two weeks of treatment. Cox proportional hazards modeling was used to identify the best predictors of switching from the initially assigned antipsychotic medication.

Results
About one-third of patients (29.5%, 191/648) switched antipsychotics before the end of the one-year study. There were six variables identified as the best predictors of switching: lack of antipsychotic use in the prior year, pre-existing depression, female gender, lack of substance use disorder, worsening of akathisia (as measured by the Barnes Akathisia Scale), and worsening of symptoms of depression/anxiety (subscale score on the Positive and Negative Syndrome Scale) during the first two weeks of antipsychotic therapy.

Conclusions
Switching antipsychotics appears to be prevalent in the naturalistic treatment of schizophrenia and can be predicted by a small and distinct set of variables. Interestingly, worsening of anxiety and depressive symptoms and of akathisia following two weeks of treatment were among the more robust predictors of subsequent switching of antipsychotics.
Glucose uptake regulation in E. coli by the small RNA SgrS: comparative analysis of E. coli K-12 (JM109 and MG1655) and E. coli B (BL21)
Authors: Negrete Alejandro , Ng Weng-Ian , Shiloach Joseph 
Published: October 2010

Abstract

Background
The effect of high glucose concentration on the transcription levels of the small RNA SgrS and the messenger RNA ptsG, (encoding the glucose transporter IICBGlc), was studied in both E. coli K-12 (MG1655 and JM109) and E. coli B (BL21). It is known that the transcription level of sgrS increases when E. coli K-12 (MG1655 and JM109) is exposed to the non-metabolized glucose alpha methyl glucoside (αMG) or when the bacteria with a defective glycolysis pathway is grown in presence of glucose. The increased level of sRNA SgrS reduces the level of the ptsG mRNA and consequently lowers the level of the glucose transporter IICBGlc. The suggested trigger for this action is the accumulation of the corresponding phospho-sugars.

Results
In the course of the described work, it was found that E. coli B (BL21) and E. coli K-12 (JM109 and MG1655) responded similarly to αMG: both strains increased SgrS transcription and reduced ptsG transcription. However, the two strains reacted differently to high glucose concentration (40 g/L). E. coli B (BL21) reacted by increasing sgrS transcription and reducing ptsG transcription while E. coli K-12 (JM109 and MG1655) did not respond to the high glucose concentration, and, therefore, transcription of sgrS was not detected and ptsG mRNA level was not affected.

Conclusions
The results suggest that E. coli B (BL21) tolerates high glucose concentration not only by its more efficient central carbon metabolism, but also by controlling the glucose transport into the cells regulated by the sRNA SgrS, which may suggest a way to control glucose consumption and increase its efficient utilization.
P2X7 receptor regulates leukocyte infiltrations in rat frontoparietal cortex following status epilepticus
Authors: Kim Ji-Eun , Ryu Hea Jin , Yeo Seong-Il , Kang Tae-Cheon 
Published: October 2010

AbstractBackgroundIn the present study, we investigated the roles of P2X7 receptor in recruitment and infiltration of neutrophil during epileptogenesis in rat epilepsy models.MethodsStatus epilepticus (SE) was induced by pilocarpine in rats that were intracerebroventricularly infused with either saline, 2',3'-O-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP), or IL-1Ra (interleukin 1 receptor antagonist) prior to SE induction. Thereafter, we performed immunohistochemical studies for myeloperoxidase (MPO), CD68, interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2).ResultsIn saline-infused animals, neutrophils and monocytes were observed in frontoparietal cortex (FPC) at 1 day and 2 days after SE, respectively. In BzATP-infused animals, infiltrations of neutrophils and monocytes into the FPC were detected at 12 hr and 1 day after SE, respectively. In OxATP-infused animals, neutrophils and monocytes infiltrated into the FPC at 1 day and 2 days after SE, respectively. However, the numbers of both classes of leukocytes were significantly lower than those observed in the saline-infused group. In piriform cortex (PC), massive leukocyte infiltration was detected in layers III/IV of saline-infused animals at 1-4 days after induction of SE. BzATP or OxATP infusion did not affect neutrophil infiltration in the PC. In addition, P2X7 receptor-mediated MCP-1 (released from microglia)/MIP-2 (released from astrocytes) regulation was related to SE-induced leukocyte infiltration in an IL-1β-independent manner.ConclusionsOur findings suggest that selective regulation of P2X7 receptor-mediated neutrophil infiltration may provide new therapeutic approaches to SE or epilepsy.