bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional profiling of the LPS induced NF-κB response in macrophages
Authors: Sharif Omar , Bolshakov Viacheslav N , Raines Stephanie , Newham Peter , Perkins Neil D 
Published: January 2007

Abstract

Background
Exposure of macrophages to bacterial products such as lipopolysaccharide (LPS) results in activation of the NF-κB transcription factor, which orchestrates a gene expression programme that underpins the macrophage-dependent immune response. These changes include the induction or repression of a wide range of genes that regulate inflammation, cell proliferation, migration and cell survival. This process is tightly regulated and loss of control is associated with conditions such as septic shock, inflammatory diseases and cancer. To study this response, it is important to have in vitro model systems that reflect the behaviour of cells in vivo. In addition, it is necessary to understand the natural differences that can occur between individuals. In this report, we have investigated and compared the LPS response in macrophage derived cell lines and peripheral blood mononuclear cell (PBMC) derived macrophages.

Results
Gene expression profiles were determined following LPS treatment of THP-1 cells for 1 and 4 hours. LPS significantly induced or repressed 72 out of 465 genes selected as being known or putative NF-κB target genes, which exhibited 4 temporal patterns of expression. Results for 34 of these genes, including several genes not previously identified as LPS target genes, were validated using real time PCR. A high correlation between microarray and real time PCR data was found. Significantly, the LPS induced expression profile of THP-1 cells, as determined using real time PCR, was found to be very similar to that of human PBMC derived macrophages. Interestingly, some differences were observed in the LPS response between the two donor PBMC macrophage populations. Surprisingly, we found that the LPS response in U937 cells was dramatically different to both THP-1 and PBMC derived macrophages.

Conclusion
This study revealed a dynamic and diverse transcriptional response to LPS in macrophages, involving both the induction and repression of gene expression in a time dependent manner. Moreover, we demonstrated that the LPS induced transcriptional response in the THP-1 cell line is very similar to primary PBMC derived macrophages. Therefore, THP-1 cells represent a good model system for studying the mechanisms of LPS and NF-κB dependent gene expression.
A procedure for the detection of linkage with high density SNP arrays in a large pedigree with colorectal cancer
Authors: Middeldorp Anneke , Jagmohan-Changur Shantie , Helmer Quinta , van der Klift Heleen M , Tops Carli MJ , Vasen Hans FA , Devilee Peter , Morreau Hans , Houwing-Duistermaat Jeanine J , Wijnen Juul T , van Wezel Tom 
Published: January 2007

Abstract

Background
The apparent dominant model of colorectal cancer (CRC) inheritance in several large families, without mutations in known CRC susceptibility genes, suggests the presence of so far unidentified genes with strong or moderate effect on the development of CRC. Linkage analysis could lead to identification of susceptibility genes in such families. In comparison to classical linkage analysis with multi-allelic markers, single nucleotide polymorphism (SNP) arrays have increased information content and can be processed with higher throughput. Therefore, SNP arrays can be excellent tools for linkage analysis. However, the vast number of SNPs on the SNP arrays, combined with large informative pedigrees (e.g. >35–40 bits), presents us with a computational complexity that is challenging for existing statistical packages or even exceeds their capacity. We therefore setup a procedure for linkage analysis in large pedigrees and validated the method by genotyping using SNP arrays of a colorectal cancer family with a known MLH1 germ line mutation.

Methods
Quality control of the genotype data was performed in Alohomora, Mega2 and SimWalk2, with removal of uninformative SNPs, Mendelian inconsistencies and Mendelian consistent errors, respectively. Linkage disequilibrium was measured by SNPLINK and Merlin. Parametric linkage analysis using two flanking markers was performed using MENDEL. For multipoint parametric linkage analysis and haplotype analysis, SimWalk2 was used.

Results
On chromosome 3, in the MLH1-region, a LOD score of 1.9 was found by parametric linkage analysis using two flanking markers. On chromosome 11 a small region with LOD 1.1 was also detected. Upon linkage disequilibrium removal, multipoint linkage analysis yielded a LOD score of 2.1 in the MLH1 region, whereas the LOD score dropped to negative values in the region on chromosome 11. Subsequent haplotype analysis in the MLH1 region perfectly matched the mutation status of the family members.

Conclusion
We developed a workflow for linkage analysis in large families using high-density SNP arrays and validated this workflow in a family with colorectal cancer. Linkage disequilibrium has to be removed when using SNP arrays, because it can falsely inflate the LOD score. Haplotype analysis is adequate and can predict the carrier status of the family members.
Tuning of Electronic Structures of Quasi-One-Dimensional Bromo-Bridged PdII–PdIV Mixed-Valence Complexes by Substituting Counter Anions
Authors: Arakawa Hisamitsu , Kawakami Daisuke , Takaishi Shinya , Kajiwara Takashi , Miyasaka Hitoshi , Sugiura Ken-ichi , Yamashita Masahiro , Kishida Hideo , Okamoto Hiroshi 
Published: January 2007

Abstract
New quasi-one-dimensional bromo-bridged PdII–PdIV mixed-valence complexes with long chain alkylsufonates [Pd(en)2][PdBr2(en)](CnH2n+1SO3)4·2H2O (en = ethylenediamine, n = 7, 8, 9, and 10) were synthesized. With increasing alkyl-chain length (n) of the counter anions, the PdII···PdIV distances decreased, indicating that the oxidation states of the Pd atoms are close to the PdIII state.
Heat and mass transfer in wood composite panels during hot pressing: Part 3. Predicted variations and interactions of the pressing variables
Authors: Yu Changming , Dai Chunping , Wang Brad Jianhe 
Published: January 2007

Abstract
As a continuation of previous publications on a physical-mathematical model of heat and mass transfer and a structural model of mat permeability, this paper presents typical prediction results for 15 pressing variables for strand mats. A case study and complete solutions to the governing equations are provided. The results show how the heat and mass transfer is controlled by heat conduction and convection involving gas flow and phase change. The model predictions provide a comprehensive illustration of the temporal and spatial variations of basic pressing variables, including mat temperature, gas pressure, moisture control and resin curing rate. The model offers a powerful tool for simulating the effects of mat structure, pressing schedule and initial mat conditions.
Properties of piezoelectric voltage considering the microscopic structure of wood cell walls
Authors: Nakai Takahisa , Yamamoto Hiroyuki 
Published: January 2007

Abstract
The combined effects of the grain-angle (θ) and the microfibril angle (MFA) on the piezoelectric voltage (P) are discussed for a wood specimen subjected to unidirectional stress. The fiber axis of the specimen investigated was not parallel to the loading direction. A theoretical discussion is provided concerning fundamental elastic equations that predict the elastic strain field in the crystalline cellulose microfibril (CMF). It was assumed that an ideal wood specimen could be represented by a multi-tracheid model consisting mainly of the middle layer of the secondary wall. Experimental results revealed that plots of the piezoelectric voltage (P) versus the grain angle (θ) show concave curves with a maximum at θ=45°, regardless of MFA in the specimen. A similar tendency was obtained for the relationship predicted between the average shear strain along the CMF and θ. The results indicate that generation of a shear strain in the CMF positively contributes to the piezoelectric effect in wood.
Quantitative analysis of somatostatin receptor subtype (SSTR1–5) gene expression levels in somatotropinomas and non-functioning pituitary adenomas
Authors: Taboada Giselle F , Luque Raul M , Bastos Wildebranham , Guimarães Renata F C , Marcondes Jorge B , Chimelli Leila M C , Fontes Rosita , Mata Paulo J P , Filho Paulo Niemeyer , Carvalho Denise P , Kineman Rhonda D , Gadelha Mônica R 
Published: January 2007

Objective: It is believed that the variable effectiveness of somatostatin analogs in post-surgical management of somatotropinomas and non-functioning pituitary adenomas (NFPA) may be due in part to variable expression of somatostatin receptor isoforms (SSTR1–5), within and between pituitary tumor types.
Design and methods: Quantitative real-time RT-PCR was used to compare absolute mRNA copy numbers for all five SSTR isoforms in 23 somatotropinomas and 19 NFPA.
Results: Somatostatin receptor subtype 5 mRNA was present at the highest level in somatotropinomas, followed by SSTR2>SSTR3≫SSTR1⋙SSTR4. In contrast, SSTR3 mRNA was present at the highest level in NFPA, followed by SSTR2, while SSTR1, SSTR4, and SSTR5 transcripts were only detectable in select tumors. Among somatotropinomas, a positive correlation was found between SSTR2 mRNA levels and the percent decrease of GH (%GH) after 3 and 6 months of therapy with octreotide long acting repeatable (LAR) (r=0.51 and r=0.66; P=0.05 and P=0.008). Also the percent decrease of IGF-I (%IGF-I) after 3 months of octreotide LAR was negatively correlated with SSTR5 and %IGF-I after 6 months of octreotide LAR was positively correlated with SSTR2.
Conclusions: The present report is a large series examining SSTR mRNA levels in somatotropinomas and NFPA. These initial findings suggest that detailed knowledge of the SSTR mRNA expression profile in somatotropinomas can help to predict the hormonal response to therapy with LAR. Also, it appears that SSTR3 in NFPA may be a potential target for SSTR3 preferential or universal ligands such as pasireotide.
Circulating ghrelin levels in girls with central precocious puberty are reduced during treatment with LHRH analog
Authors: Maffeis Claudio , Franceschi Roberto , Moghetti Paolo , Camilot Marta , Lauriola Silvana , Tatò Luciano 
Published: January 2007

Decreased levels of ghrelin have been measured in growing children during puberty. No data are available for girls with central precocious puberty (CPP).
Aims: To explore ghrelin changes before, during, and after GnRH analog treatment in girls with CPP.
Subjects and methods: A sample of 20 Caucasian girls (8.08 ± 0.65 years of age) with CPP was recruited. Height and weight, bone age, LH, FSH, 17β estradiol (E2), and ghrelin were measured before starting treatment with GnRH analog, 18 months after therapy began and again 6 months after therapy discontinuation.
Results: LH and E2 serum levels decreased significantly during treatment (2.45 ± 2.03 vs 0.67 ± 0.49 UI/l, P < 0.01 and 28.17 ± 9.7 vs 15 pmol/l, P < 0.01 respectively), returning to baseline levels after the discontinuation of therapy (4.75 ± 1.66 UI/l and 29.23 ± 6.99 pmol/l respectively). LH peaked following LHRH stimulation significantly (P < 0.01) decreased during treatment (24.45 ± 14.17 vs 1.3 ± 0.18 UI/l) and then increased after therapy discontinuation (12.58 ± 6.09, P < 0.01). Ghrelin decreased significantly (P < 0.05) during treatment (1849 ± 322 vs 1207 ± 637 pg/ml), and increased, though not significantly (P = 0.09) after therapy withdrawal (1567 ± 629 pg/ml).
Conclusions: Contrary to what is expected in physiologic puberty, where ghrelin is progressively reduced, the prepubertal hormone milieau induced by GnRHa treatment in patients suffering from central precocious puberty (CPP) did not promote an increase in ghrelin circulating levels. Therefore, in CPP, ghrelin secretion seems to be independent from pubertal development per se. Concomitant estrogen suppression during treatment may play a potential role in the regulation of ghrelin secretion in these girls.
A Cassette System to Study Embryonic Stem Cell Differentiation by Inducible RNA Interference
Authors: Wegmüller Daniel , Raineri Ines , Gross Brigitte , Oakeley Edward J. , Moroni Christoph 
Published: January 2007

Abstract
Although differentiation of pluripotent embryonic stem cells is restricted by a hierarchy of transcription factors, little is known about whether post-transcriptional mechanisms similarly regulate early embryoid differentiation. We developed a system where small hairpin (sh)RNAs can be induced in embryonic stem (ES) cells from a defined locus following integration by Flp recombinase-mediated DNA recombination. To verify the system, the key transcription factor Stat3, which maintains pluripotency, was downregulated by shRNA, and the expected morphological and biochemical markers of differentiation were observed. Induction of shRNA specific for the post-transcriptional regulator Brf1 (Zfp36L1) amplified the cardiac markers with strong stimulation of cardiomyocyte formation within embryoid bodies. These findings identify Brf1 as a novel potential regulator of cardiomyocyte formation and suggest that post-transcriptional mechanisms are of importance to early development and, possibly, to regenerative medicine. The inducible RNA interference system presented here should also allow assignment of function for candidate genes with suspected roles in ES cell development.
Disclosure of potential conflicts of interest is found at the end of this article.
Brain Transplantation of Immortalized Human Neural Stem Cells Promotes Functional Recovery in Mouse Intracerebral Hemorrhage Stroke Model
Authors: Lee Hong J. , Kim Kwang S. , Kim Eun J. , Choi Hyun B. , Lee Kwang H. , Park In H. , Ko Yong , Jeong Sang W. , Kim Seung U. 
Published: January 2007

Abstract
We have generated stable, immortalized cell lines of human NSCs from primary human fetal telencephalon cultures via a retroviral vector encoding v-myc. HB1.F3, one of the human NSC lines, expresses a normal human karyotype of 46, XX, and nestin, a cell type-specific marker for NSCs. F3 has the ability to proliferate continuously and differentiate into cells of neuronal and glial lineage. The HB1.F3 human NSC line was used for cell therapy in a mouse model of intracerebral hemorrhage (ICH) stroke. Experimental ICH was induced in adult mice by intrastriatal administration of bacterial collagenase; 1 week after surgery, the rats were randomly divided into two groups so as to receive intracerebrally either human NSCs labeled with β-galactosidase (n = 31) or phosphate-buffered saline (PBS) (n = 30). Transplanted NSCs were detected by 5-bromo-4-chloro-3-indolyl-β-d-galactoside histochemistry or double labeling with β-galactosidase (β-gal) and mitogen-activated protein (MAP)2, neurofilaments (both for neurons), or glial fibrillary acidic protein (GFAP) (for astrocytes). Behavior of the animals was evaluated for period up to 8 weeks using modified Rotarod tests and a limb placing test. Transplanted human NSCs were identified in the perihematomal areas and differentiated into neurons (β-gal/MAP2+ and β-gal/NF+) or astrocytes (β-gal/GFAP+). The NSC-transplanted group showed markedly improved functional performance on the Rotarod test and limb placing after 2–8 weeks compared with the control PBS group (p &lt; .001). These results indicate that the stable immortalized human NSCs are a valuable source of cells for cell replacement and gene transfer for the treatment of ICH and other human neurological disorders.
Disclosure of potential conflicts of interest is found at the end of this article.
Mesenchymal Stem Cells Regulate Angiogenesis According to Their Mechanical Environment
Authors: Kasper Grit , Dankert Niels , Tuischer Jens , Hoeft Moritz , Gaber Timo , Glaeser Juliane D. , Zander Desiree , Tschirschmann Miriam , Thompson Mark , Matziolis Georg , Duda Georg N. 
Published: January 2007

Abstract
In fracture and bone defect healing, MSCs largely drive tissue regeneration. MSCs have been shown to promote angiogenesis both in vivo and in vitro. Angiogenesis is a prerequisite to large tissue reconstitution. The present study investigated how mechanical loading of MSCs influences their proangiogenic capacity. The results show a significant enhancement of angiogenesis by conditioned media from mechanically stimulated compared with unstimulated MSCs in two-dimensional tube formation and three-dimensional spheroid sprouting assays. In particular, proliferation but not migration or adhesion of endothelial cells was elevated. Promotion of angiogenesis was dependent upon fibroblast growth factor receptor 1 (FGFR1) signaling. Moreover, stimulation of tube formation was inhibited by vascular endothelial growth factor receptor (VEGFR) tyrosine kinase blocking. Screening for the expression levels of different soluble regulators of angiogenesis revealed an enrichment of matrix metalloprotease 2, transforming growth factor β1, and basic fibroblast growth factor but not of vascular endothelial growth factor in response to mechanical stimulation. In conclusion, mechanical loading of MSCs seems to result in a paracrine stimulation of angiogenesis, most likely by the regulation of a network of several angiogenic molecules. The underlying mechanism appears to be dependent on the FGFR and VEGFR signaling cascades and might be mediated by an additional cross-talk with other pathways.
Disclosure of potential conflicts of interest is found at the end of this article.
Progenitor Cells from the Porcine Neural Retina Express Photoreceptor Markers After Transplantation to the Subretinal Space of Allorecipients
Authors: Klassen Henry , Kiilgaard Jens Folke , Zahir Tasneem , Ziaeian Boback , Kirov Ivan , Scherfig Erik , Warfvinge Karin , Young Michael J. 
Published: January 2007

Abstract
Work in rodents has shown that cultured retinal progenitor cells (RPCs) integrate into the degenerating retina, thus suggesting a potential strategy for treatment of similar degenerative conditions in humans. To demonstrate the relevance of the rodent work to large animals, we derived progenitor cells from the neural retina of the domestic pig and transplanted them to the laser-injured retina of allorecipients. Prior to grafting, immunocytochemical analysis showed that cultured porcine RPCs widely expressed neural cell adhesion molecule, as well as markers consistent with immature neural cells, including nestin, Sox2, and vimentin. Subpopulations expressed the neurodevelopmental markers CD-15, doublecortin, β-III tubulin, and glial fibrillary acidic protein. Retina-specific markers expressed included the bipolar marker protein kinase Cα and the photoreceptor-associated markers recoverin and rhodopsin. In addition, reverse transcription-polymerase chain reaction showed expression of the transcription factors Dach1, Hes1, Lhx2, Pax6, Six3, and Six6. Progenitor cells prelabeled with vital dyes survived as allografts in the subretinal space for up to 5 weeks (11 of 12 recipients) without exogenous immune suppression. Grafted cells expressed transducin, recoverin, and rhodopsin in the pig subretinal space, suggestive of differentiation into photoreceptors or, in a few cases, migrated into the neural retina and extended processes, the latter typically showing radial orientation. These results demonstrate that many of the findings seen with rodent RPCs can be duplicated in a large mammal. The pig offers a number of advantages over mice and rats, particularly in terms of functional testing and evaluation of the potential for clinical translation to human subjects.
Disclosure of potential conflicts of interest is found at the end of this article.
Transcription Profiling of Adult and Fetal Human Neuroprogenitors Identifies Divergent Paths to Maintain the Neuroprogenitor Cell State
Authors: Maisel Martina , Herr Alexander , Milosevic Javorina , Hermann Andreas , Habisch Hans-Jörg , Schwarz Sigrid , Kirsch Matthias , Antoniadis Gregor , Brenner Rolf , Hallmeyer-Elgner Susanne , Lerche Holger , Schwarz Johannes , Storch Alexander 
Published: January 2007

Abstract
Global gene expression profiling was performed using RNA from adult human hippocampus-derived neuroprogenitor cells (NPCs) and multipotent frontal cortical fetal NPCs compared with adult human mesenchymal stem cells (hMSCs) as a multipotent adult stem cell control, and adult human hippocampal tissue, to define a gene expression pattern that is specific for human NPCs. The results were compared with data from various databases. Hierarchical cluster analysis of all neuroectodermal cell/tissue types revealed a strong relationship of adult hippocampal NPCs with various white matter tissues, whereas fetal NPCs strongly correlate with fetal brain tissue. However, adult and fetal NPCs share the expression of a variety of genes known to be related to signal transduction, cell metabolism and neuroectodermal tissue. In contrast, adult NPCs and hMSCs overlap in the expression of genes mainly involved in extracellular matrix biology. We present for the first time a detailed transcriptome analysis of human adult NPCs suggesting a relationship between hippocampal NPCs and white matter-derived precursor cells. We further provide a framework for standardized comparative gene expression analysis of human brain-derived NPCs with other stem cell populations or differentiated tissues.
Disclosure of potential conflicts of interest is found at the end of this article.
Chronic Myeloid Leukemia Blast Crisis Arises from Progenitors
Authors: Michor Franziska 
Published: January 2007

Abstract
Chronic myeloid leukemia (CML) progresses through three distinct clinical stages: chronic phase, accelerated phase, and blast crisis. The progression to accelerated phase and blast crisis is driven by activation of oncogenes, inactivation of tumor suppressor genes, and/or amplification of the BCR-ABL fusion gene, which causes the chronic phase of the disease. The cell of origin of blast crisis is a subject of speculation. Here, I develop a simple mathematical model of CML blast crisis to investigate whether blasts arise from leukemic stem cells or more differentiated leukemic cells. I use data of patients treated with imatinib and previous agents to estimate the effects of therapy on the rate of progression. Imatinib reduces the progression rate 10-fold as compared with previous (ineffective) therapies. If blasts were produced by leukemic stem cells, there would be no difference in the rate of progression between patients treated with imatinib and previous therapies, because imatinib seems to be incapable of depleting leukemic stem cells. Imatinib does, however, deplete leukemic progenitors. Therefore, CML blasts are likely to arise from leukemic progenitors.
Disclosure of potential conflicts of interest is found at the end of this article.
Erasure of Cellular Memory by Fusion with Pluripotent Cells
Authors: Do Jeong Tae , Han Dong Wook , Gentile Luca , Sobek-Klocke Ingeborg , Stehling Martin , Lee Hoon Taek , Schöler Hans R. 
Published: January 2007

Abstract
Pluripotent cells have been suggested as a prime source to reprogram somatic cells. We used F9 EC cells as a pluripotent partner to reprogram neurosphere cells (NSCs) because they exhibit a nonneural differentiation potential in the presence of retinoic acid. F9-NSC hybrid cells displayed various features of reprogramming, such as reactivation of pluripotency genes, inactivation of tissue-specific genes, and reactivation of the inactive X chromosome. As the hybrid cells undergo differentiation, the pluripotency markers Oct4 and Nanog were downregulated. Whereas neural marker genes were not upregulated, endodermal and mesodermal markers were, suggesting that NSCs lose memory of their neural origin and preferentially differentiate to the lineages corresponding to the F9 program. After fusion, the methylation status in the Xist region was similar to that of F9 EC cells. However, upon differentiation, the Xist region failed to resume the methylation patterns of differentiated cells, suggesting that the Xist in F9-NSC hybrids does not easily acquire a differentiated state.
Disclosure of potential conflicts of interest is found at the end of this article.