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Factor Genes (factor + gene)
Kinds of Factor Genes Terms modified by Factor Genes Selected AbstractsNovel Magnetic Hydroxyapatite Nanoparticles as Non-Viral Vectors for the Glial Cell Line-Derived Neurotrophic Factor GeneADVANCED FUNCTIONAL MATERIALS, Issue 1 2010Hsi-Chin Wu Abstract Nanoparticles (NPs) of synthetic hydroxyapatite (Hap) and natural bone mineral (NBM) are rendered magnetic by treatment with iron ions using a wet-chemical process. The magnetic NPs (mNPs), which are about 300,nm in diameter, display superparamagnetic properties in a superconducting quantum interference device, with a saturation magnetization of about 30,emu g,1. X-ray diffraction and transmission electron microscopy reveal that the magnetic properties of the NPs are the result of the hetero-epitaxial growth of magnetite on the Hap and NBM crystallites. The mNPs display a high binding affinity for plasmid DNA in contrast to magnetite NPs which do not bind the plasmid well. The mHap and mNBM NPs result in substantial increases in the transfection of rat marrow-derived mesenchymal stem cells with the gene for glial cell line-derived neurotrophic factor (GDNF), with magnetofection compared to transfection in the absence of a magnet. The amount of GDNF recovered in the medium approaches therapeutic levels despite the small amount of plasmid delivered by the NPs. [source] GATA factors as key regulatory molecules in the development of Drosophila endodermDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 9 2005Ryutaro Murakami Essential roles for GATA factors in the development of endoderm have been reported in various animals. A Drosophila GATA factor gene, serpent (srp, dGATAb, ABF), is expressed in the prospective endoderm, and loss of srp activity causes transformation of the prospective endoderm into ectodermal foregut and hindgut, indicating that srp acts as a selector gene to specify the developmental fate of the endoderm. While srp is expressed in the endoderm only during early stages, it activates a subsequent GATA factor gene, dGATAe, and the latter continues to be expressed specifically in the endoderm throughout life. dGATAe activates various functional genes in the differentiated endodermal midgut. An analogous mode of regulation has been reported in Caenorhabditis elegans, in which a pair of GATA genes, end-1/3, specifies endodermal fate, and a downstream pair of GATA genes, elt-2/7, activates genes in the differentiated endoderm. Functional homology of GATA genes in nature is apparently extendable to vertebrates, because endodermal GATA genes of C. elegans and Drosophila induce endoderm development in Xenopus ectoderm. These findings strongly imply evolutionary conservation of the roles of GATA factors in the endoderm across the protostomes and the deuterostomes. [source] Transcriptional control of the pvdS iron starvation sigma factor gene by the master regulator of sulfur metabolism CysB in Pseudomonas aeruginosaENVIRONMENTAL MICROBIOLOGY, Issue 6 2010Francesco Imperi Summary In the Gram-negative pathogen Pseudomonas aeruginosa, the alternative sigma factor PvdS acts as a key regulator of the response to iron starvation. PvdS also controls P. aeruginosa virulence, as it drives the expression of a large set of genes primarily implicated in biogenesis and transport of the pyoverdine siderophore and synthesis of extracellular factors, such as protease PrpL and exotoxin A. Besides the ferric uptake regulatory protein Fur, which shuts off pvdS transcription under iron-replete conditions, no additional regulatory factor(s) controlling the pvdS promoter activity have been characterized so far. Here, we used the promoter region of pvdS as bait to tentatively capture, by DNA-protein affinity purification, P. aeruginosa proteins that are able to bind specifically to the pvdS promoter. This led to the identification and functional characterization of the LysR-like transcription factor CysB as a novel regulator of pvdS transcription. The CysB protein directly binds to the pvdS promoter in vitro and acts as a positive regulator of PvdS expression in vivo. The absence of a functional CysB protein results in about 50% reduction of expression of PvdS-dependent virulence phenotypes. Given the role of CysB as master regulator of sulfur metabolism, our findings establish a novel molecular link between the iron and sulfur regulons in P. aeruginosa. [source] Genetic mapping of Foxb1-cell lineage shows migration from caudal diencephalon to telencephalon and lateral hypothalamusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2008Tianyu Zhao Abstract The hypothalamus is a brain region with vital functions, and alterations in its development can cause human disease. However, we still do not have a complete description of how this complex structure is put together during embryonic and early postnatal stages. Radially oriented, outside-in migration of cells is prevalent in the developing hypothalamus. In spite of this, cell contingents from outside the hypothalamus as well as tangential hypothalamic migrations also have an important role. Here we study migrations in the hypothalamic primordium by genetically labeling the Foxb1 diencephalic lineage. Foxb1 is a transcription factor gene expressed in the neuroepithelium of the developing neural tube with a rostral expression boundary between caudal and rostral diencephalon, and therefore appropriate for marking migrations from caudal levels into the hypothalamus. We have found a large, longitudinally oriented migration stream apparently originating in the thalamic region and following an axonal bundle to end in the anterior portion of the lateral hypothalamic area. Additionally, we have mapped a specific expansion of the neuroepithelium into the rostral diencephalon. The expanded neuroepithelium generates abundant neurons for the medial hypothalamus at the tuberal level. Finally, we have uncovered novel diencephalon-to-telencephalon migrations into septum, piriform cortex and amygdala. [source] The full spectrum of holoprosencephaly-associated mutations within the ZIC2 gene in humans predicts loss-of-function as the predominant disease mechanism,,HUMAN MUTATION, Issue 4 2009Erich Roessler Abstract Mutations of the ZIC2 transcription factor gene are among the most common heterozygous variations detected in holoprosencephaly (HPE) patients, a patient group who lack critical midline forebrain specification due to defective embryonic signaling during development. Recent studies indicate that complete deficiency of the related murine Zic2 transcription factor can also be a contributing factor to variable midline deficiencies, presenting during mid-gastrulation, that could explain similar forebrain anomalies in this model system. Here we collect and summarize all available mutations in the human ZIC2 gene detected in HPE patients (21 published and 62 novel). Our analysis corroborates this mechanism proposed in mice by predicting loss-of-function as the likely pathogenetic mechanism common to most, if not all, of these mutations in HPE. Published 2009 Wiley-Liss, Inc. [source] A genetic polymorphism in the coding region of the gastric intrinsic factor gene (GIF) is associated with congenital intrinsic factor deficiency,HUMAN MUTATION, Issue 1 2004Marilyn M. Gordon Abstract Congenital intrinsic factor (IF) deficiency is a disorder characterized by megaloblastic anemia due to the absence of gastric IF (GIF, GenBank NM_005142) and GIF antibodies, with probable autosomal recessive inheritance. Most of the reported patients are isolated cases without genetic studies of the parents or siblings. Complete exonic sequences were determined from the PCR products generated from genomic DNA of five affected individuals. All probands had the identical variant (g.68A>G) in the second position of the fifth codon in the coding sequence of the gene that introduces a restriction enzyme site for Msp I and predicts a change in the mature protein from glutamine5 (CAG) to arginine5 (CGG). Three subjects were homozygous for this base exchange and two subjects were heterozygous, one of which was apparently a compound heterozygote at positions 1 and 2 of the fifth codon ([g.67C>G] + [g.68A>G]). The other patient, heterozygous for position 2, had one heterozygous unaffected parent. Most parents were heterozygous for this base exchange, confirming the pattern of autosomal recessive inheritance for congenital IF deficiency. cDNA encoding GIF was mutated at base pair g.68 (A>G) and expressed in COS-7 cells. The apparent size, secretion rate, and sensitivity to pepsin hydrolysis of the expressed IF were similar to native IF. The allelic frequency of g.68A>G was 0.067 and 0.038 in two control populations. This sequence aberration is not the cause of the phenotype, but is associated with the genotype of congenital IF deficiency and could serve as a marker for inheritance of this disorder. Hum Mutat 23:85,91, 2004. © 2003 Wiley-Liss, Inc. [source] The hinge region fragment of immunoglobulin G improves immunogenicity of recombinant gonadotrophin-releasing hormone conjugated to the T-helper epitope in designing peptide vaccinesIMMUNOLOGY, Issue 1pt2 2009Jinshu Xu Summary In our previous study, the hinge fragment (225,232/225,,232,) of human immunoglobulin G1 (IgG1) was used as a space peptide linker for synthesizing the GnRH3,hinge,MVP chimeric peptide, whereby three repeated gonadotrophin-releasing hormone (GnRH) units and a T-cell epitope from measles virus fusion protein (MVP) were amide-bond-linked at the N and C terminus, respectively, to the hinge peptide for producing anti-GnRH antibody responses. To investigate whether or not the hinge region fragment can improve the immunogenicity of GnRH, we further synthesized and purified GnRH3,hinge,MVP, GnRH3,hinge and GnRH3,MVP using recombinant DNA technology. Under high pH conditions, GnRH3,hinge,MVP was capable of forming double-chain structures. Immunization of male mice with the immunogens of GnRH3,hinge,MVP resulted in the generation of high-titre antibodies specific for GnRH. The synthetic GnRH3,hinge and GnRH3,MVP induced a lower titre of anti-GnRH antibody than GnRH3,hinge,MVP. This was followed by a decrease in serum testosterone levels, which resulted in a low level of expression of the relaxin-like factor gene in the testis. Our data suggest that peptide and T-cell epitopes oriented at the N-terminus or C-terminus of hinge peptides simplify the antigenic peptide conjugates and may be considered as potential synthetic immunogens. [source] Pituitary Transcription Factors: From Congenital Deficiencies to Gene TherapyJOURNAL OF NEUROENDOCRINOLOGY, Issue 9 2006M. H. Quentien Despite the existence of interspecies phenotypic variability, animal models have yielded valuable insights into human pituitary diseases. Studies on Snell and Jackson mice known to have growth hormone, prolactin and thyroid-stimulating hormone deficiencies involving the hypoplastic pituitary gland have led to identifying alterations of the pituitary specific POU homeodomain Pit-1 transcription factor gene. The human phenotype associated with rare mutations in this gene was found to be similar to that of these mice mutants. Terminal differentiation of lactotroph cells and direct regulation of the prolactin gene both require interactions between Pit-1 and cell type specific partners, including panpituitary transcriptional regulators such as Pitx1 and Pitx2. Synergistic activation of the prolactin promoter by Pitx factors and Pit-1 is involved not only in basal condition, but also in responsiveness to forskolin, thyrotrophin-releasing-hormone and epidermal growth factor. In corticotroph cells, Pitx1 interacts with Tpit. Tpit mutations have turned out to be the main molecular cause of neonatal isolated adrenocorticotrophin deficiency. This finding supports the idea that Tpit plays an essential role in the differentiation of the pro-opiomelanocortin pituitary lineage. The effects of Pit-1 are not restricted to hormone gene regulation because this factor also contributes to cell division and protects the cell from programmed cell death. Lentiviral vectors expressing a Pit-1 dominant negative mutant induced time- and dose-dependent cell death in somatotroph and lactotroph adenomas in vitro. Gene transfer by lentiviral vectors should provide a promising step towards developing an efficient specific therapeutic approach by which a gene therapy programme for treating human pituitary adenomas could be based. [source] Expression studies on a novel type 2B variant of the von Willebrand factor gene (R1308L) characterized by defective collagen bindingJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2005L. BARONCIANI Summary., A novel mutation, R1308L (3923G > T) was present in the heterozygous state in five members of a family with type 2B von Willebrand disease (VWD) characterized by a full set of von Willebrand factor (VWF) multimers in plasma and by the absence of thrombocytopenia before and after desmopressin (DDAVP). The defect (R1308L) was located at the same amino acid position of one of the most common mutations associated with type 2B VWD (R1308C), which is characterized by the loss of high molecular weight VWF multimers (HMWM) in plasma and the occurrence of thrombocytopenia. To understand the mechanisms of this defect, the novel (R1308L) and ,common' (R1308C) mutations were expressed in COS-7 cells, either alone or, to mimic the patients' heterozygous state, together with wild-type VWF. R1308L recombinant VWF (rVWF) had a higher affinity for the platelet glycoprotein Ib, (GPIb,) receptor than wild-type rVWF, R1308C rVWF showing an even higher affinity. A novel finding was that both mutant rVWFs showed a similarly reduced binding to collagen type I and type III in comparison with wild-type rVWF. The latter finding suggests a more important role than recognized so far for the VWF A1 domain in VWF binding to collagen, which may contribute to the in vivo hemostatic defect associated with type 2B VWD. [source] Molecular tumor markers for asbestos-related mesothelioma: Serum diagnostic markersPATHOLOGY INTERNATIONAL, Issue 11 2006Masahiro Maeda Mesothelioma is an aggressive tumor arising from the mesothelium, and is usually associated with previous exposure to asbestos. The incubation period of the tumor may be described as 30,40 years, and the prognosis is dismal. In addition to immunohistochemical markers, recently, serum markers for the diagnosis of mesothelioma have been reported as candidates. In contrast, the expression in renal carcinoma (ERC) gene has been discovered in the Eker rat model (Tsc2 gene mutant), which is a homolog of the human mesothelin/megakaryocyte potentiating factor gene, and a novel ELISA system (N-ERC/mesothelin) has been developed. It has also been found that N-ERC/mesothelin is very stable and plentiful in the blood. In the present paper the potential utility of molecular diagnostic markers is reviewed, including ELISA systems for asbestos-related mesothelioma. [source] Probing Pineal-specific Gene Expression with Transgenic Zebrafish,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 4 2008Daisuke Kojima The pineal gland of zebrafish (Danio rerio) contains light-sensitive photoreceptor cells and plays an important role in the neuroendocrine system. The zebrafish exorhodopsin gene encodes a pineal-specific photoreceptive protein, whose promoter region harbors a cis -acting element, pineal expression-promoting element (PIPE), directing pineal-specific gene expression. For in vivo genetic studies on PIPE-binding proteins and their regulatory mechanisms, we generated a transgenic zebrafish line, Tg(P20 -rh/P:gfp), that expresses green fluorescent protein (GFP) under the control of the zebrafish rhodopsin promoter fused with 20 PIPE repeats. In Tg(P20 -rh/P:gfp) fish, PIPE-dependent gene expression is visualized by GFP fluorescence in the pineal gland along with PIPE-independent GFP signals in the retinal rod photoreceptors. The transgenic fish exhibit detectable and reproducible GFP fluorescence in the larval pineal gland by 5 days postfertilization. Antisense morpholino-mediated knock-down of a pineal transcription factor gene, otx5, suppresses pineal GFP expression in the transgenic line. In a pilot screen of N -ethyl- N -nitrosourea-treated fish of the GFP transgenic line, we isolated potential dominant mutations that cause attenuation of pineal GFP fluorescence with a marginal effect on the retinal GFP signal. The results suggest that the Tg(P20 -rh/P:gfp) line will be useful for detecting deficits in PIPE-dependent gene expression in the pineal gland. [source] Prefrontal cognition in schizophrenia and bipolar illness in relation to Val66Met polymorphism of the brain-derived neurotrophic factor genePSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 1 2006JANUSZ K. RYBAKOWSKI md Abstract, The measures of prefrontal cognition have been used as endophenotype in molecular-genetic studies. Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive functions and in the pathogenesis of major psychoses. This study investigates the relationship between Val66Met polymorphisms of the BDNF gene and prefrontal cognitive function in 129 patients with schizophrenia and 111 patients with bipolar mood disorder. Cognitive tests included the Wisconsin Card Sorting Test (WCST), with such domains as number of perseverative errors, non-perseverative errors, completed corrected categories, conceptual level responses, and set to the first category, and the N-back test, where mean reaction time and percent of correct reactions were measured. Genotyping for Val66Met BDNF polymorphism was done by polymerase chain reaction method. In schizophrenia, no relationship between Val66Met polymorphism of the BDNF gene and the results of the WCST was observed. Patients with Val/Val genotype had a higher percentage of correct reactions in the N-back test than those with the remaining genotypes. Bipolar patients with Val/Val genotype obtained significantly better results on three of five domains of the WCST. No relationship between BDNF polymorphism and the results of the N-back test was found in this group. A limitation to the results could be variable psychopathological state and medication during cognitive testing and lack of Hardy,Weinberg equilibrium in schizophrenia group. Val66Met polymorphism of the BDNF gene may be associated with cognitive performance on the WCST in bipolar mood disorder but not in schizophrenia. An association of this polymorphism with performance on the N-back test in schizophrenia and not in bipolar illness may suggest that in schizophrenia, the BDNF system may be connected with early phases of information processing. [source] ANAC012, a member of the plant-specific NAC transcription factor family, negatively regulates xylary fiber development in Arabidopsis thalianaTHE PLANT JOURNAL, Issue 6 2007Jae-Heung Ko Summary Vascular plants evolved to have xylem that provides physical support for their growing body and serves as a conduit for water and nutrient transport. In a previous study, we used comparative-transcriptome analyses to select a group of genes that were upregulated in xylem of Arabidopsis plants undergoing secondary growth. Subsequent analyses identified a plant-specific NAC-domain transcription factor gene (ANAC012) as a candidate for genetic regulation of xylem formation. Promoter-GUS analyses showed that ANAC012 expression was preferentially localized in the (pro)cambium region of inflorescence stem and root. Using yeast transactivation analyses, we confirmed the function of ANAC012 as a transcriptional activator, and identified an activation domain in the C terminus. Ectopic overexpression of ANAC012 in Arabidopsis (35S::ANAC012 plants) dramatically suppressed secondary wall deposition in the xylary fiber and slightly increased cell-wall thickness in the xylem vessels. Cellulose compositions of the cell wall were decreased in the inflorescent stems and roots of 35S::ANAC012 plants, probably resulting from defects in xylary fiber formation. Our data suggest that ANAC012 may act as a negative regulator of secondary wall thickening in xylary fibers. [source] Functional and prognostic relevance of the ,173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 5 2003Fabrizio De Benedetti Objective To address the functional and prognostic relevance of the ,173 single-nucleotide G-to-C polymorphism of the macrophage migration inhibitory factor (MIF) gene in patients with systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) by evaluating its association with serum and synovial fluid levels of MIF, with glucocorticoid requirement, and with the outcome of the disease. Methods A total of 136 patients with systemic-onset JIA were studied, including 98 patients from the British Paediatric Rheumatology Study Group's National Repository for JIA and 38 patients who were followed up at the IRCCS Policlinico San Matteo (Pavia, Italy) and the IRCCS G. Gaslini (Genoa, Italy). The MIF-173 polymorphism was genotyped using SnaPshot ddNTP primer extension and capillary electrophoresis. MIF levels were measured by enzyme-linked immunosorbent assay. The evaluation of the association of the MIF-173 polymorphism with outcome was performed only in Italian patients who were followed up for >5 years, by analyzing retrospectively 1) the number of joints with active arthritis and the number of joints with limited range of motion; 2) the score, at the last visit, on the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ); and 3) data concerning the treatment regimens during the disease course. Results Systemic-onset JIA patients carrying a MIF-173*C allele had serum and synovial fluid levels of MIF significantly higher than those in patients with the GG genotype. The duration of glucocorticoid treatment on a daily regimen was significantly longer in patients carrying a MIF-173*C allele than in MIF-173 GG homozygous patients. Moreover, the duration of clinical response to intraarticular injection of triamcinolone hexacetonide was significantly shorter in patients carrying a MIF-173*C allele. At the last visit, the numbers of joints with active arthritis, the C-HAQ scores, and the numbers of joints with limited range of motion were significantly higher in patients carrying the MIF-173*C allele. Conclusion Our study shows the functional relevance of the MIF-173 polymorphism and suggests that the MIF-173*C allele is a predictor of poor outcome in systemic-onset JIA. [source] Mutation screening of the macrophage migration inhibitory factor gene: Positive association of a functional polymorphism of macrophage migration inhibitory factor with juvenile idiopathic arthritisARTHRITIS & RHEUMATISM, Issue 9 2002Rachelle Donn Objective To determine if polymorphisms of the macrophage migration inhibitory factor (MIF) gene are associated with juvenile idiopathic arthritis (JIA). Methods Denaturing high-performance liquid chromatography was used to screen the MIF gene in 32 UK Caucasian controls and 88 UK Caucasian JIA patients. Ninety-two healthy UK Caucasian controls were then genotyped for each of the polymorphic positions identified. A panel of 526 UK Caucasian JIA patients and 259 UK Caucasian controls were subsequently genotyped for a single-nucleotide polymorphism (SNP) identified in the 5,-flanking region of the gene, using SNaPshot ddNTP primer extension and capillary electrophoresis. The functional significance of this polymorphism was also studied using luciferase-based reporter gene assays in human T lymphoblast and epithelial cell lines. Results A tetranucleotide repeat CATT(5,7) beginning at nucleotide position ,794 and 3 SNPs at positions ,173 (G to C), +254 (T to C), and +656 (C to G) of the MIF gene were identified. No JIA-specific mutations were found. Allele and genotype frequencies differed significantly between the controls and the JIA patients for the MIF-173 polymorphism. Individuals possessing a MIF-173*C allele had an increased risk of JIA (34.8% versus 21.6%) (odds ratio 1.9, 95% confidence interval 1.4,2.7; P = 0.0002). Furthermore, the MIF-173* G and C variants resulted in altered expression of MIF in a cell type,specific manner. Serum levels of MIF were also significantly higher in individuals who carried a MIF-173*C allele (P = 0.04). Conclusion The ,173-MIF*C allele confers increased risk of susceptibility to JIA. Our data suggest a cell type,specific regulation of MIF, which may be central to understanding its role in inflammation. [source] Association between brain-derived neurotrophic factor gene and a severe form of bipolar disorder, but no interaction with the serotonin transporter geneBIPOLAR DISORDERS, Issue 5 2008Ilona Vincze Background:, Recent data suggest that brain-derived neurotrophic factor (BDNF) and the serotonergic system are involved and interact in major depressive disorder and suicidal behavior (SB). Several family and population-based studies have reported associations between the BDNF gene and serotonin-related genes, specifically the serotonin transporter (5HTT) gene, with bipolar disorder (BD) and SB. However, despite the fact that gene-by-gene interaction between BDNF and 5HTT has been demonstrated in monoamine deficiencies in animals, this kind of interaction has never been tested in humans. Our hypothesis is that some BDNF and 5HTT polymorphisms might confer increased risk for BD and SB and that both genes may interact with each other. Methods:, To test this hypothesis, we genotyped the most common BDNF polymorphisms, G196A (Val66Met), A-633T and BDNF-LCPR, as well as 5HTT (5HTT-LPR), in 447 BD patients and 370 controls. Results:, We replicated the association previously reported between BDNF G196A (Val66Met) polymorphism and BD. We also observed a correlation between the number of G196 alleles and short alleles of 5HTT-LPR and the severity of SB in BD. However, we found no significant interaction between these two markers. Conclusions:, These results suggest that BDNF G196A as well as 5HTT-LPR polymorphisms confer risk for SB in BD, but we did not observe any evidence for an interaction between them. [source] Distinguishing between type 2B and pseudo-von Willebrand disease and its clinical importanceBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2006Mohammad S. Enayat Summary Pseudo-von Willebrand disease (p-VWD) and type 2B von Willebrand disease (VWD) have similar phenotypic parameters and clinical symptoms, but different aetiologies. Fourteen individuals from five families with a historical diagnosis of type 2B VWD but with no mutation in the von Willebrand factor gene were re-investigated for the possibility of p-VWD, using platelet aggregation in the presence of cryoprecipitate. p-VWD was confirmed by targeted DNA sequencing of the glycoprotein Ib, gene, identifying a heterozygous Glycine 233 Valine substitution. This study suggests that p-VWD may be under diagnosed, and that platelet aggregation in the presence of cryoprecipitate is useful in differentiating this disorder from type 2B VWD. [source] Factor VIII deficiency not induced by FVIII gene mutation in a female first cousin of two brothers with haemophilia ABRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2002Claudine Mazurier Summary. In this study, we reinvestigated a 20-year-old woman, the first cousin of two brothers with severe haemophilia A. This patient was previously assumed to be a carrier of haemophilia A due to her FVIII deficiency. We identified a novel FVIII gene mutation in the family and demonstrated that the FVIII deficiency in this female patient did not result from this gene mutation, but was linked to molecular defects in the von Willebrand factor gene. [source] Sox genes regulate type 2 collagen expression in avian neural crest cellsDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 8 2006Takashi Suzuki Neural crest cells give rise to a wide variety of cell types, including cartilage cells in the cranium and neurons and glial cells in the peripheral nervous system. To examine the relationship of cartilage differentiation and neural crest differentiation, we examined the expression of Col2a1, which encodes type 2 collagen often used as a cartilage marker, and compared it with the expression of Sox transcription factor genes, which are involved in neural crest development and chondrogenesis. We found that Col2a1 is expressed in many neural crest-derived cell types along with combinations of Sox9, Sox10 and LSox5. Overexpression studies reveal the activation of Col2a1 expression by Sox9 and Sox10, and cross-regulation of these Sox genes. Luciferase assay indicates a direct activation of the Col2a1 enhancer/promoter both by Sox9 and Sox10, and this activation is further enhanced by cAMP-dependent kinase (PKA) signaling. Our study suggests that the regulatory mechanisms are similar in cartilage and neural crest differentiation. [source] Sequential activation of transcription factors in lens inductionDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 5 2000Hajime Ogino Since the pioneering work of the early 1900s, the lens has been used as a model system for the study of tissue development in vertebrates. A number of embryological transplantation experiments designed to elucidate the role of tissue interactions in the formation of the lens have led to the proposal of a stepwise determination model. This model has recently been refined through the identification of certain transcription factor genes, which exhibit distinct expression patterns and functional properties in the lens cell lineage. Otx2, Pax6, and Lens1 are induced by the adjacent anterior neural plate and expressed in predifferentiated lens ectoderm. Contact between the optic vesicle and lens ectoderm promotes expression of mafs, Soxs, and Prox1, which are responsible for the initiation of lens differentiation programs including crystallin expression, cell elongation, and cell cycle arrest. Further analysis of the expression and functional characteristics of these transcription factors will allow greater detail when describing the orchestration of genetic programs, which control tissue development from induction to maturation. [source] Comparative expression analysis of transcription factor genes in the endostyle of invertebrate chordatesDEVELOPMENTAL DYNAMICS, Issue 3 2005Jin Hiruta Abstract The endostyle of invertebrate chordates is a pharyngeal organ that is thought to be homologous with the follicular thyroid of vertebrates. Although thyroid-like features such as iodine-concentrating and peroxidase activities are located in the dorsolateral part of both ascidian and amphioxus endostyles, the structural organization and numbers of functional units are different. To estimate phylogenetic relationships of each functional zone with special reference to the evolution of the thyroid, we have investigated, in ascidian and amphioxus, the expression patterns of thyroid-related transcription factors such as TTF-2/FoxE4 and Pax2/5/8, as well as the forkhead transcription factors FoxQ1 and FoxA. Comparative gene expression analyses depicted an overall similarity between ascidians and amphioxus endostyles, while differences in expression patterns of these genes might be specifically related to the addition or elimination of a pair of glandular zones. Expressions of Ci-FoxE and BbFoxE4 suggest that the ancestral FoxE class might have been recruited for the formation of thyroid-like region in a possible common ancestor of chordates. Furthermore, coexpression of FoxE4, Pax2/5/8, and TPO in the dorsolateral part of both ascidian and amphioxus endostyles suggests that genetic basis of the thyroid function was already in place before the vertebrate lineage. Developmental Dynamics 233:1031,1037, 2005. © 2005 Wiley-Liss, Inc. [source] Long-term depression activates transcription of immediate early transcription factor genes: involvement of serum response factor/Elk-1EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006Antje Lindecke Abstract Long-term depression (LTD) is one of the paradigms used in vivo or ex vivo for studying memory formation. In order to identify genes with potential relevance for memory formation we used mouse organotypic hippocampal slice cultures in which chemical LTD was induced by applications of 3,5-dihydroxyphenylglycine (DHPG). The induction of chemical LTD was robust, as monitored electrophysiologically. Gene expression analysis after chemical LTD induction was performed using cDNA microarrays containing >7000 probes. The DHPG-induced expression of immediate early genes (c-fos, junB, egr1 and nr4a1) was subsequently verified by TaqMan polymerase chain reaction. Bioinformatic analysis suggested a common regulator element [serum response factor (SRF)/Elk-1 binding sites] within the promoter region of these genes. Indeed, here we could show a DHPG-dependent binding of SRF at the SRF response element (SRE) site within the promoter region of c-fos and junB. However, SRF binding to egr1 promoter sites was constitutive. The phosphorylation of the ternary complex factor Elk-1 and its localization in the nucleus of hippocampal neurones after DHPG treatment was shown by immunofluorescence using a phosphospecific antibody. We suggest that LTD leads to SRF/Elk-1-regulated gene expression of immediate early transcription factors, which could in turn promote a second broader wave of gene expression. [source] Gene networks controlling early cerebral cortex arealizationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006Antonello Mallamaci Abstract Early thalamus-independent steps in the process of cortical arealization take place on the basis of information intrinsic to the cortical primordium, as proposed by Rakic in his classical protomap hypothesis [Rakic, P. (1988)Science, 241, 170,176]. These steps depend on a dense network of molecular interactions, involving genes encoding for diffusible ligands which are released around the borders of the cortical field, and transcription factor genes which are expressed in graded ways throughout this field. In recent years, several labs worldwide have put considerable effort into identifying members of this network and disentangling its topology. In this respect, a considerable amount of knowledge has accumulated and a first, provisional description of the network can be delineated. The aim of this review is to provide an organic synthesis of our current knowledge of molecular genetics of early cortical arealization, i.e. to summarise the mechanisms by which secreted ligands and graded transcription factor genes elaborate positional information and trigger the activation of distinctive area-specific morphogenetic programs. [source] Chromosome band 16q22-linked familial AML: Exclusion of candidate genes, and possible disease risk modification by NQO1 polymorphismsGENES, CHROMOSOMES AND CANCER, Issue 3 2004Robert Escher Analyses of chromosomal translocation and inversion breakpoints in sporadic acute myeloid leukemias have identified many transcription factors as playing a role in leukemogenesis. Studies of families with a Mendelian predisposition to hematological malignancies have identified the gene coding for the transcription factor RUNX1 as a leukemia-predisposing gene involved in the first steps of leukemogenesis. Using two families, another autosomal dominant familial leukemia locus was linked to chromosome band 16q22 where the CBFB gene maps. Although CBFB forms a core-binding factor transcriptional complex with RUNX1, previous analyses have excluded the CBFB gene as the leukemia-predisposing gene in these families. In the current study, we performed an extended molecular analysis in these families of the four other transcription factor genes in the 16q22 critical region as well as of two other genes with a known association with leukemia. Several previously undescribed but nonpathogenic sequence variants were identified. We demonstrated that the transcription factors E2F4, CTCF, NFATC3, and NFAT5, and the genes coding for NAD(P)H:quinone oxido-reductase 1 (NQO1) and for E-cadherin are not responsible for the leukemia susceptibility in these families. The presence of NQO1 polymorphisms may suggest a role for this gene in disease risk modification in these families. © 2004 Wiley-Liss, Inc. [source] Differential identification of Bacillus anthracis from environmental Bacillus species using microarray analysisJOURNAL OF APPLIED MICROBIOLOGY, Issue 4 2006J.E. Burton Abstract Aims:, To determine whether microarray analysis could be employed for the differential identification of a range of environmental Bacillus sp. from four strains of Bacillus anthracis. Methods and Results:, Oligonucleotide probes were designed that were specific to virulence factor genes of B. anthracis (pag, lef and cap), the variable number tandem repeat region of the B. anthracis vrrA gene and to the 16S-23S rRNA intergenic transcribed spacer region (ITS) and pleiotropic regulator (plcR) regions of the Bacillus cereus subgroup species. Generic probes were also designed to hybridize with conserved regions of the 16S rRNA genes of Bacillus (as a positive control), Neisseria sp., Pseudomonas sp., Streptococcus sp., Mycobacterium sp. and to all members of the Enterobacteriaceae to allow simultaneous detection of these bacteria. Identification of B. anthracis was found to rely entirely on hybridization of DNA specific to regions of the pag, lef and cap genes. Cross-reaction was observed between B. anthracis and other Bacillus species with all the other Bacillus probes tested. Results obtained using microarray hybridizations were confirmed using conventional microbiological techniques and found to have very high comparability. Conclusions:, Microarray-based assays are an effective method for the identification of B. anthracis from mixed-culture environmental samples without problems of false-positivity that have been observed with conventional PCR assays. Significance and Impact of the Study:, Identification of environmental Bacillus sp. by conventional PCR is prone to potential for reporting false-positives. This study provides a method for the exclusion of such isolates. [source] Microarray analysis of transcription factor gene expression in melatonin-treated human peripheral blood mononuclear cellsJOURNAL OF PINEAL RESEARCH, Issue 4 2006Eunyoung Ha Abstract:, The existence of specific melatonin-binding sites in lymphoid cells led to the discovery of signal transduction pathway for melatonin in human lymphocytes and immunomodulatory role of melatonin in immune cells. In recent years, transcriptional regulation of melatonin on various transcription factors has been demonstrated. Therefore, this study was designed to assess by cDNA microarray analysis the regulatory effects of melatonin on transcription factors in human peripheral blood mononuclear cells (PBMCs). Forty-six genes were upregulated and 23 were downregulated more than twofold in melatonin-treated PBMCs. Of the more than twofold upregulated transcription factor genes, homeo box A4 (HOXA4), forkhead box O1A (FOXO1A), transcription elongation factor B (SIII), polypeptide 3 (TCEB3), and peroxisome proliferative activated receptor delta (PPARD) were identified. Of the more than twofold downregulated genes, PHD finger protein 15 (PHF15) and zinc finger protein 33a (ZNF33A) were identified. In summary, identification of these genes by cDNA microarray analysis in response to melatonin administration may provide a foundation for further studies on the function of melatonin in human PBMCs. [source] Maturation-Dependent Alcohol Resistance in the Developing Mouse: Cerebellar Neuronal Loss and Gene Expression During Alcohol-Vulnerable and -Resistant PeriodsALCOHOLISM, Issue 8 2008Bahri Karaçay Background:, Alcohol abuse during pregnancy injures the fetal brain. One of alcohol's most important neuroteratogenic effects is neuronal loss. Rat models have shown that the cerebellum becomes less vulnerable to alcohol-induced neuronal death as it matures. We determined if maturation-dependent alcohol resistance occurs in mice and compared patterns of gene expression during the alcohol resistant and sensitive periods. Methods:, Neonatal mice received alcohol daily over postnatal day (PD) 2 to 4 or PD8 to 10. Purkinje cells and granule cells were quantified on PD25. The temporal expression patterns of 4 neuro-developmental genes and 3 neuro-protective genes in the cerebellum were determined daily over PD0 to 15 to determine how gene expression changes as the cerebellum transitions from alcohol-vulnerable to alcohol-resistant. The effect of alcohol on expression of these genes was determined when the cerebellum is alcohol sensitive (PD4) and resistant (PD10). Results:, Purkinje and granule cells were vulnerable to alcohol-induced death at PD2 to 4, but not at PD8 to 10. Acquisition of maturation-dependent alcohol resistance coincided with changes in the expression of neurodevelopmental genes. The vulnerability of cerebellar neurons to alcohol toxicity declined in parallel with decreasing levels of Math1 and Cyclin D2, markers of immature granule cells. Likewise, the rising resistance to alcohol toxicity paralleled increasing levels of GABA ,-6 and Wnt-7a, markers of mature granule neurons. Expression of growth factors and genes with survival promoting function (IGF-1, BDNF, and cyclic AMP response element binding protein) did not rise as the cerebellum transitioned from alcohol-vulnerable to alcohol-resistant. All 3 were expressed at substantial levels during the vulnerable period and were not expressed at higher levels later. Acute alcohol exposure altered the expression of neurodevelopmental genes and growth factor genes when administered either during the alcohol vulnerable period or resistant period. However, the patterns in which gene expression changed varied among the genes and depended on timing of alcohol administration. Conclusions:, Mice have a temporal window of vulnerability in the first week of life, during which cerebellar neurons are more sensitive to alcohol toxicity than during the second week. Expression of genes governing neuronal maturation changes in synchrony with the acquisition of alcohol resistance. Growth factors do not rise as the cerebellum transitions from alcohol-vulnerable to alcohol-resistant. Thus, a process intrinsic to neuronal maturation, rather than rising levels of growth factors, likely underlies maturation-dependent alcohol resistance. [source] Priming of plant innate immunity by rhizobacteria and ,-aminobutyric acid: differences and similarities in regulationNEW PHYTOLOGIST, Issue 2 2009Sjoerd Van der Ent Summary ,,Pseudomonas fluorescens WCS417r bacteria and ,-aminobutyric acid can induce disease resistance in Arabidopsis, which is based on priming of defence. ,,In this study, we examined the differences and similarities of WCS417r- and ,-aminobutyric acid-induced priming. ,,Both WCS417r and ,-aminobutyric acid prime for enhanced deposition of callose-rich papillae after infection by the oomycete Hyaloperonospora arabidopsis. This priming is regulated by convergent pathways, which depend on phosphoinositide- and ABA-dependent signalling components. Conversely, induced resistance by WCS417r and ,-aminobutyric acid against the bacterial pathogen Pseudomonas syringae are controlled by distinct NPR1-dependent signalling pathways. As WCS417r and ,-aminobutyric acid prime jasmonate- and salicylate-inducible genes, respectively, we subsequently investigated the role of transcription factors. A quantitative PCR-based genome-wide screen for putative WCS417r- and ,-aminobutyric acid-responsive transcription factor genes revealed distinct sets of priming-responsive genes. Transcriptional analysis of a selection of these genes showed that they can serve as specific markers for priming. Promoter analysis of WRKY genes identified a putative cis -element that is strongly over-represented in promoters of 21 NPR1-dependent, ,-aminobutyric acid-inducible WRKY genes. ,,Our study shows that priming of defence is regulated by different pathways, depending on the inducing agent and the challenging pathogen. Furthermore, we demon-strated that priming is associated with the enhanced expression of transcription factors. [source] Variation of freezing tolerance, Cor/Lea gene expression and vernalization requirement in Japanese common wheatPLANT BREEDING, Issue 5 2007M. Ishibashi Abstract Freezing tolerance and vernalization requirement are important traits for adaptation of wheat to growing in a high-latitude area. Fr-1 and Vrn-1, tightly linked on homoeologous group 5 chromosomes, are major loci for controlling the freezing tolerance and vernalization requirement, respectively. It was previously supposed that winter-habit wheat should possess a winter-type Fr-1 allele guaranteeing winter survival, but that such allele is unnecessary for spring-habit cultivars. To clarify such allelic linkage between the Vrn-1 and Fr-1 loci in the D genome, we studied freezing tolerance and vernalization requirement, and compared cold-responsive expression patterns of Cor (cold responsive)/Lea (late-embryogenesis-abundant), their putative transcription factor genes and three Vrn-1 homoeologs in Japanese common wheat cultivars. Wide variation of freezing tolerance and two alleles of Vrn-D1 were observed in the Japanese cultivars, whereas the accumulation levels of the Cor/Lea transcripts were not be correlated with the levels of freezing tolerance. The allelic linkage between Vrn-1 and Fr-1 loci well known in the A genome was not observed in the D genome of Japanese cultivars possessing Vrn-D1 or vrn-D1 allele. [source] The soybean Dof-type transcription factor genes, GmDof4 and GmDof11, enhance lipid content in the seeds of transgenic Arabidopsis plantsTHE PLANT JOURNAL, Issue 4 2007Hui-Wen Wang Summary Soybean is one of the most important leguminous seed crops among the oil crops. Although the pathways for lipid biosynthesis have been identified, the factors that regulate the biosynthetic pathways at the transcriptional level are largely unknown. Here, we report our findings on the involvement of soybean Dof-type transcription factor genes in the regulation of the lipid content in soybean seeds. We identified 28 Dof-type transcription factor genes in soybean plants, and these genes displayed diverse patterns of expression in various organs. Seven flower/pod-specific genes and one constitutively expressed gene were further investigated. The proteins encoded by these seven genes were localized in the nucleus, and exhibited different abilities for transcriptional activation and DNA binding. Two genes, GmDof4 and GmDof11, were found to increase the content of total fatty acids and lipids in GmDof4 and GmDof11 transgenic Arabidopsis seeds. We also found that the 1000-seed weight was increased in the GmDof4 and GmDof11 transgenic plants. Using microarray and DNA binding analysis, we found that the two Dof-like proteins, GmDof4 and GmDof11, activated the acetyl CoA carboxylase gene and long-chain-acyl CoA synthetase gene, respectively, by direct binding to the cis -DNA elements in their promoter regions. In addition, both proteins downregulated the storage protein gene, CRA1, through direct binding. These results suggest that the two GmDof genes may augment the lipid content of soybean seeds by upregulating genes that are associated with the biosynthesis of fatty acids. [source] | |||||||||||||||||||||||||