Home About us Contact
|
Home About us Contact | ||
|
|
||
Homolog
Kinds of Homolog Selected AbstractsOverexpression of degenerative spermatocyte homolog 1 up-regulates the expression of cyclin D1 and enhances metastatic efficiency in esophageal carcinoma Eca109 cells,MOLECULAR CARCINOGENESIS, Issue 10 2009Wu Zhou Abstract Cyclin D1 plays a pivotal role in cell-cycle transition through G1 phase. In this article, we found that Degenerative Spermatocyte Homolog 1 (DEGS1) up-regulated the expression of cyclin D1 and the activation of transcription factor NF-,B was essential for DEGS1-induced cyclin D1 production. Forced expression of DEGS1 in Esophageal carcinoma cell line Eca109 cells increased their ability of cell migration and significantly induced tumor metastasis in nude mice, whereas RNA interference-mediated knockdown of DEGS1 cells significantly inhibited cell migration in vitro, as well as tumor metastasis in vivo. Our results demonstrated that expression of DEGS1 up-regulated the expression of cyclin D1 and enhanced the efficiency of tumor metastasis. © 2009 Wiley-Liss, Inc. [source] Birth defects caused by mutations in human GLI3 and mouse Gli3 genesCONGENITAL ANOMALIES, Issue 1 2010Ichiro Naruse ABSTRACT GLI3 is the gene responsible for Greig cephalopolysyndactyly syndrome (GCPS), Pallister,Hall syndrome (PHS) and Postaxial polydactyly type-A (PAP-A). Genetic polydactyly mice such as Pdn/Pdn (Polydactyly Nagoya), XtH/XtH (Extra toes) and XtJ/XtJ (Extra toes Jackson) are the mouse homolog of GCPS, and Gli3tmlUrtt/Gli3tmlUrt is produced as the mouse homolog of PHS. In the present review, relationships between mutation points of GLI3 and Gli3, and resulting phenotypes in humans and mice are described. It has been confirmed that mutation in the upstream or within the zinc finger domain of the GLI3 gene induces GCPS; that in the post-zinc finger region including the protease cleavage site induces PHS; and that in the downstream of the GLI3 gene induces PAP-A. A mimicking phenomenon was observed in the mouse homolog. Therefore, human GLI3 and mouse Gli3 genes have a common structure, and it is suggested here that mutations in the same functional regions produce similar phenotypes in human and mice. The most important issue might be that GCPS and PHS exhibit an autosomal dominant trait, but mouse homologs, such as Pdn/Pdn, XtH/XtH, XtJ/XtJ and Gli3tmlUrt/Gli3tmlUrt, are autosomal recessive traits in the manifestation of similar phenotypes to human diseases. It is discussed here how the reduced amounts of the GLI3 protein, or truncated mutant GLI3 protein, disrupt development of the limbs, head and face. [source] Further delineation of 9q22 deletion syndrome associated with basal cell nevus (Gorlin) syndrome: Report of two cases and review of the literatureCONGENITAL ANOMALIES, Issue 1 2009Kayono Yamamoto ABSTRACT Basal cell nevus syndrome (BCNS; Gorlin syndrome) is an autosomal dominant disorder, characterized by a predisposition to neoplasms and developmental abnormalities. BCNS is caused by mutations in the human homolog of the Drosophila patched gene-1, PTCH1, which is mapped on chromosome 9q22.3. Nonsense, frameshift, in-frame deletions, splice-site, and missense mutations have been found in the syndrome. Haploinsufficiency of PTCH1, which is caused by interstitial deletion of 9q22.3, is also responsible for the syndrome. To date, 19 cases with interstitial deletion of long arm of chromosome 9 involving the region of q22 have been reported. We describe two unrelated patients with some typical features of BCNS associated with deletion of 9q21.33-q31.1 and determined the boundary of the deletion by fluorescence in situ hybridization (FISH) with bacterial artificial chromosome (BAC) clones. The results showed that the size of deletions is between 15.33 and 16.04 Mb in patient 1 and between 18.08 and 18.54 Mb in patient 2. Although the size and breakpoints were different from those of previously reported cases, the clinical features are common to patients with 9q22 deletion associated with BCNS. Delineation of the 9q22 deletions and further consideration of the genes responsible for the characteristic manifestations may provide insight into this newly recognized deletion syndrome. [source] Increased fat oxidation and regulation of metabolic genes with ultraendurance exerciseACTA PHYSIOLOGICA, Issue 1 2007J. W. Helge Abstract Aim:, Regular endurance exercise stimulates muscle metabolic capacity, but effects of very prolonged endurance exercise are largely unknown. This study examined muscle substrate availability and utilization during prolonged endurance exercise, and associated metabolic genes. Methods:, Data were obtained from 11 competitors of a 4- to 5-day, almost continuous ultraendurance race (seven males, four females; age: 36 ± 11 years; cycling o2peak: males 57.4 ± 5.9, females 48.1 ± 4.0 mL kg,1 min,1). Before and after the race muscle biopsies were obtained from vastus lateralis, respiratory gases were sampled during cycling at 25 and 50% peak aerobic power output, venous samples were obtained, and fat mass was estimated by bioimpedance under standardized conditions. Results:, After the race fat mass was decreased by 1.6 ± 0.4 kg (11%; P < 0.01). Respiratory exchange ratio at the 25 and 50% workloads decreased (P < 0.01) from 0.83 ± 0.06 and 0.93 ± 0.03 before, to 0.71 ± 0.01 and 0.85 ± 0.02, respectively, after the race. Plasma fatty acids were 3.5 times higher (from 298 ± 74 to 1407 ± 118 ,mol L,1; P < 0.01). Muscle glycogen content fell 50% (from 554 ± 28 to 270 ± 25 nmol kg,1 d.w.; n = 7, P < 0.01), whereas the decline in muscle triacylglycerol (from 32 ± 5 to 22 ± 3 mmol kg,1 d.w.; P = 0.14) was not statistically significant. After the race, muscle mRNA content of lipoprotein lipase and glycogen synthase increased (P < 0.05) 3.9- and 1.7-fold, respectively, while forkhead homolog in rhabdomyosarcoma, pyruvate dehydrogenase kinase 4 and vascular endothelial growth factor mRNA tended (P < 0.10) to be higher, whereas muscle peroxisome proliferator-activated receptor , co-activator-1, mRNA tended to be lower (P = 0.06). Conclusion:, Very prolonged exercise markedly increases plasma fatty acid availability and fat utilization during exercise. Exercise-induced regulation of genes encoding proteins involved in fatty acid recruitment and oxidation may contribute to these changes. [source] XBtg2 is required for notochord differentiation during early Xenopus developmentDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 7 2005Kaoru Sugimoto The notochord is essential for normal vertebrate development, serving as both a structural support for the embryo and a signaling source for the patterning of adjacent tissues. Previous studies on the notochord have mostly focused on its formation and function in early organogenesis but gene regulation in the differentiation of notochord cells itself remains poorly defined. In the course of screening for genes expressed in developing notochord, we have isolated Xenopus homolog of Btg2 (XBtg2). The mammalian Btg2 genes, Btg2/PC3/TIS21, have been reported to have multiple functions in the regulation of cell proliferation and differentiation but their roles in early development are still unclear. Here we characterized XBtg2 in early Xenopus laevis embryogenesis with focus on notochord development. Translational inhibition of XBtg2 resulted in a shortened and bent axis phenotype and the abnormal structures in the notochord tissue, which did not undergo vacuolation. The XBtg2-depleted notochord cells expressed early notochord markers such as chordin and Xnot at the early tailbud stage, but failed to express differentiation markers of notochord such as Tor70 and 5-D-4 antigens in the later stages. These results suggest that XBtg2 is required for the differentiation of notochord cells such as the process of vacuolar formation after determination of notochord cell fate. [source] Possible role of Hes5 for the rostrocaudal polarity formation of the tectumDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 3 2004Jun Kimura The alar plate of the mesencephalon differentiates into the optic tectum. Retinal fibers project to the tectum topographically in a retinotopic manner. Engrailed (En) is responsible for the tectum polarity formation and regionalization. Former study indicated the presence of the molecule whose expression is repressed by En and that represses the isthmus-related gene expression. To isolate such molecules, we constructed a subtracted library between cDNA population of the normal rostral mesencephalon and of the rostral mesencephalon that misexpresses En2. From the library, we isolated cHes5, a chicken homolog of Drosophila hairy/Enhancer of split. cHes5 begins to be expressed in the rostral part of the E2 mesencephalon, and spreads to caudal mesencephalon by E3. To our expectation, cHes5 expression was repressed by En2. Furthermore, misexpression of cHes5 in the mesencephalon inhibited expression of ephrinA2, a marker of caudal mesencephalon. An active repressor form of Hes5, which is a chimeric molecule of Hes5 and repressor domain of En2, showed a similar but more severe phenotype. The results indicate that Hes5 is regulated by En and is responsible for rostral identity of mesencephalon by repressing ephrinA2. [source] Spatio-temporal expression of Xenopus vasa homolog, XVLG1, in oocytes and embryos: The presence of XVLG1 RNA in somatic cells as well as germline cellsDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 2 2000Kohji Ikenishi The expression of Xenopus vasa homolog or XVLG1 was examined in oocytes and embryos by whole-mount in situ hybridization and reverse transcription,polymerase chain reaction (RT-PCR). To confirm the results in embryos, both methods were also applied to explants of germ plasm-bearing cells (GPBC) from 32-cell embryos and to those of partial embryos deprived of GPBC. By hybridization, XVLG1 ribonucleic acid (RNA) was shown to be present throughout the cytoplasm in oocytes at stages I,III, except for the mitochondrial cloud. It was barely recognizable in a portion of germline cells of embryos at specific stages, notwithstanding that XVLG1 protein was present in those cells almost throughout their life-span. A weak signal for the RNA was detectable in some of the presumptive primordial germ cells (pPGC, descendants of GPBC from the gastrula stage onward) from the late gastrula (stage 12) to the hatching tadpole stage (stage 33/34), and in some of the PGC at stages 49,50. The results for pPGC were confirmed by the hybridization of explants of GPBC at equivalent stages in control embryos. In contrast, XVLG1 RNA was detected in certain somatic cells of embryos until stage 46. These observations were supported in part by the results of RT-PCR for embryos and explants. The possible role of the product of XVLG1 was reconsidered given its presence in both germline and somatic cells. [source] Functional retinoid receptors in budding ascidiansDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 1 2000Mika Kamimura A homolog of retinoid X receptors (RXR), named PmRXR, was cloned from the budding ascidian, Polyandrocarpa misakiensis. Gel-shift assays revealed that PmRXR and a previously identified P. misakiensis retinoic acid receptor (PmRAR) formed a complex to bind vertebrate-type retinoic acid response element (RARE). Transfection assays were carried out using a reporter gene containing a RARE upstream of lacZ. Two chimeric effector genes were constructed by placing PmRXR and PmRAR cDNA fragments (containing the DNA-binding, ligand-binding and ligand-dependent transactivation domains) downstream of the human RXR, and RAR, cDNA (covering the N-terminal coding region), respectively. Each chimeric cDNA was ligated to a notochord-specific enhancer. In case the embryos were transfected with all three transgenes and treated with retinoic acid (RA), the reporter gene was activated in the notochord cells. The result suggests that the PmRXR/PmRAR complex functions as an RA-dependent transcriptional activator. The PmRXR mRNA was detected in a mesenchymal cell type, called glomerulocyte, in the developing Polyandrocarpa bud. As this cell type has been shown to express PmRAR mRNA, it seems possible that the PmRXR/PmRAR complex mediates RA signaling in this cell type to induce the expression of genes involved in the morphogenesis of the developing bud. [source] Cath6, a bHLH atonal family proneural gene, negatively regulates neuronal differentiation in the retinaDEVELOPMENTAL DYNAMICS, Issue 9 2010Fumi Kubo Abstract Basic helix,loop,helix (bHLH) transcription factors play important roles in cell type specification and differentiation during the development of the nervous system. In this study, we identified a chicken homolog of Atonal 8/ath6 (Cath6) and examined its role in the developing retina. Unlike other Atonal-family proneural genes that induce neuronal differentiation, Cath6 was expressed in stem cell-like progenitor cells in the marginal region of the retina, and its overexpression inhibited neuronal differentiation. A Cath6 fused with a VP16 transactivation domain recapitulated the inhibitory effect of Cath6 on neuronal differentiation, indicating that Cath6 functions as a transcription activator. These results demonstrate that Cath6 constitutes a unique member of the Atonal-family of genes in that it acts as a negative regulator of neuronal differentiation. Developmental Dynamics 239:2492,2500, 2010. © 2010 Wiley-Liss, Inc. [source] Asator, a tau-tubulin kinase homolog in Drosophila localizes to the mitotic spindleDEVELOPMENTAL DYNAMICS, Issue 12 2009Hongying Qi Abstract We have used a yeast two-hybrid interaction assay to identify Asator, a tau-tubulin kinase homolog in Drosophila that interacts directly with the spindle matrix protein Megator. Using immunocytochemical labeling by an Asator-specific mAb as well as by transgenic expression of a GFP-labeled Asator construct, we show that Asator is localized to the cytoplasm during interphase but redistributes to the spindle region during mitosis. Determination of transcript levels using qRT-PCR suggested that Asator is expressed throughout development but at relatively low levels. By P-element excision, we generated a null or strong hypomorphic Asatorexc allele that resulted in complete adult lethality when homozygous, indicating that Asator is an essential gene. That the observed lethality was caused by impaired Asator function was further supported by the partial restoration of viability by transgenic expression of Asator-GFP in the Asatorexc homozygous mutant background. The finding that Asator localizes to the spindle region during mitosis and directly can interact with Megator suggests that its kinase activity may be involved in regulating microtubule dynamics and microtubule spindle function. Developmental Dynamics 238:3248,3256, 2009. © 2009 Wiley-Liss, Inc. [source] Oligonucleotide-based microarray analysis of retinoic acid target genes in the protochordate, Ciona intestinalisDEVELOPMENTAL DYNAMICS, Issue 4 2005Tomoko Ishibashi Abstract Oligonucleotide-based microarray analyses were carried out to identify retinoic acid target genes in embryos of the ascidian Ciona intestinalis. Of 21,938 spots, 50 (corresponding to 43 genes) showed over twofold up-regulation in retinoic acid-treated tail bud embryos. In situ hybridization verified retinoic acid-induced up-regulation of 23 genes. Many of them were expressed in the anterior tail region, where a retinaldehyde dehydrogenase homolog is expressed. Homologs of vertebrate genes involved in neurogenesis and/or neuronal functions (e.g., COUP-TF, Ci-Hox1, and SCO-spondin) were expressed in the central nervous system of Ciona embryos, and activated by retinoic acid. Genes encoding transcription factors (e.g., Ci-lmx1.2, vitamin D receptor, and Hox proteins) and apoptosis-related proteins (e.g., transglutaminase and an apoptosis-inducing factor homolog) were also activated by retinoic acid. Simultaneous treatment of embryos with retinoic acid and puromycin revealed a few direct targets, including genes encoding Ci-Hox1, Ci-Cyp26, and an Rnf126-like ring finger protein. Developmental Dynamics 233:1571,1578, 2005. © 2005 Wiley-Liss, Inc. [source] Expression of zebrafish six1 during sensory organ development and myogenesisDEVELOPMENTAL DYNAMICS, Issue 4 2004Dmitri A. Bessarab Abstract Drosophila sine oculis homologous genes in vertebrates are homeobox-containing transcription factors functioning within the Pax-Six-Eya-Dach regulatory network during development. In this study, we describe the cloning and expression of a zebrafish homolog of sine oculis, six1. The reverse transcription-polymerase chain reaction demonstrated accumulation of six1 transcripts at mid-gastrula, and in situ hybridization showed their subsequent expression in the cranial placode and later in the olfactory, otic, and lateral line placodes, inner ear, and neuromasts. In addition, six1 is expressed in the pituitary, branchial arches, somites, pectoral fin, ventral abdomen muscle, and the cranial muscles of the eye and lower jaw. An increase of six1 expression was observed in the lateral line, muscles, and inner ear of the mind bomb mutant, illustrating a regulatory effect of the Notch pathway on expression of Six genes. Developmental Dynamics 230:781,786, 2004 © 2004 Wiley-Liss, Inc. [source] Functional analysis in Drosophila indicates that the NBCCS/PTCH1 mutation G509V results in activation of smoothened through a dominant-negative mechanismDEVELOPMENTAL DYNAMICS, Issue 4 2004Gary R. Hime Abstract Mutations in the human homolog of the patched gene are associated with the developmental (and cancer predisposition) condition Nevoid Basal Cell Carcinoma Syndrome (NBCCS), as well as with sporadic basal cell carcinomas. Most mutations that have been identified in the germline of NBCCS patients are truncating or frameshift mutations, with amino acid substitutions rarely found. We show that a missense mutation in the sterol-sensing domain G509V acts as a dominant negative when assayed in vivo in Drosophila. Ectopic expression of a Drosophila patched transgene, carrying the analogous mutation to G509V, causes ectopic activation of Hedgehog target genes and ectopic membrane stabilisation of Smoothened. The G509V transgene behaves in a manner similar, except in its subcellular distribution, to a C-terminal truncation that has been characterised previously as a dominant-negative protein. G509V exhibits vesicular localisation identical to the wild-type protein, but the C-terminal truncated Patched molecule is localised predominantly to the plasma membrane. This finding suggests that dominant-negative function can be conferred by interruption of different aspects of Patched protein behaviour. Another mutation at the same residue, G509R, did not exhibit dominant-negative activity, suggesting that simple removal of the glycine at 509 is not sufficient to impart dominant-negative function. Developmental Dynamics 229:780,790, 2004. © 2004 Wiley-Liss, Inc. [source] Timeless in lung morphogenesisDEVELOPMENTAL DYNAMICS, Issue 1 2003Jing Xiao Abstract The Clock gene, timeless, regulates circadian rhythm in Drosophila, but its vertebrate homolog is critical to embryonic development. Timeless was shown to be involved in murine urethral bud branching morphogenesis. We generated a polyclonal antibody to mouse TIMELESS (mTIM) and studied its distribution and its potential role during lung development, which also requires branching morphogenesis. In the early mouse embryo, TIM was localized to all organs, especially the neural epithelium. In embryonic day (E) 9.5 embryos, TIM was present in both epithelial and mesenchymal cells at the onset of lung morphogenesis. In E15 embryos, TIM decreased in the mesenchyme but remained pronounced in the epithelium of both large and small airways. Later, TIM was localized to a specific subset of epithelial cells with alveolar type 2 phenotype. This finding was verified by immunostaining of isolated alveolar type 2 cells. In the proximal airways, TIM was colocalized with CCSP to nonciliated columnar epithelial cells. Antisense oligonucleotides to mTim specifically inhibited branching morphogenesis of embryonic lungs in explant culture without affecting SpC expression an alveolar type 2 cell marker. In cultured lung cells, expression of TIM is independent of cell cycle and proliferation. These studies indicate that the function of Timeless is highly conserved in organs whose formation requires branching morphogenesis. Developmental Dynamics 228:82,94, 2003. © 2003 Wiley-Liss, Inc. [source] Apparent mitochondrial asymmetry in Xenopus eggsDEVELOPMENTAL DYNAMICS, Issue 4 2003Natalia Volodina Abstract Cell polarity is manifest along the animal/vegetal axis in eggs of the frog, Xenopus laevis. Along this axis, maternal cytoplasmic components are asymmetrically distributed and are thought to underlie specification of distinct cell fates. To ascertain the molecular identities of such cytoplasmic components, we have used a monoclonal antibody that specifically stains the vegetal hemisphere of Xenopus eggs. The antigenic protein Vp67 (vegetal protein of 67 kDa) was identified through purification and cloning as a Xenopus homolog of the mitochondrial protein dihydrolipoamide acetyltransferase, a component of the pyruvate dehydrogenase complex. The identification of Vp67 as a mitochondrial protein could indicate that populations of mitochondria are asymmetrically distributed in Xenopus eggs. Developmental Dynamics 226:654,662, © 2003 Wiley-Liss, Inc. [source] An amphioxus winged helix/forkhead gene, AmphiFoxD: Insights into vertebrate neural crest evolutionDEVELOPMENTAL DYNAMICS, Issue 3 2002Jr-Kai Yu Abstract During amphioxus development, the neural plate is bordered by cells expressing many genes with homologs involved in vertebrate neural crest induction. However, these amphioxus cells evidently lack additional genetic programs for the cell delaminations, migrations, and differentiations characterizing definitive vertebrate neural crest. We characterize an amphioxus winged helix/forkhead gene (AmphiFoxD) closely related to vertebrate FoxD genes. Phylogenetic analysis indicates that the AmphiFoxD is basal to vertebrate FoxD1, FoxD2, FoxD3, FoxD4, and FoxD5. One of these vertebrate genes (FoxD3) consistently marks neural crest during development. Early in amphioxus development, AmphiFoxD is expressed medially in the anterior neural plate as well as in axial (notochordal) and paraxial mesoderm; later, the gene is expressed in the somites, notochord, cerebral vesicle (diencephalon), and hindgut endoderm. However, there is never any expression in cells bordering the neural plate. We speculate that an AmphiFoxD homolog in the common ancestor of amphioxus and vertebrates was involved in histogenic processes in the mesoderm (evagination and delamination of the somites and notochord); then, in the early vertebrates, descendant paralogs of this gene began functioning in the presumptive neural crest bordering the neural plate to help make possible the delaminations and cell migrations that characterize definitive vertebrate neural crest. © 2002 Wiley-Liss, Inc. [source] Drosophila cdk5 is needed for locomotive behavior and NMJ elaboration, but seems dispensable for synaptic transmissionDEVELOPMENTAL NEUROBIOLOGY, Issue 6 2009Alexander E. Kissler Abstract Cyclin-dependent kinase 5 (Cdk5) functions in postmitotic neuronal cells and play roles in cell differentiation, cell migration, axonal guidance, and synaptic function. Here, we demonstrate that Drosophila cdk5 is dispensable for adult viability and fertility, a feature that allows us to study its physiological function in the whole animal model. For the adult, cdk5 is needed for proper locomotion and flight performance. Larvae lacking cdk5 in the presynaptic tissue display abnormal crawling motion, and their neuromuscular junctions (NMJ) are elongated and contain a higher number of boutons that are smaller. As a result of these two counteracting effects, the total synaptic area/NMJ is similar to wild type, leading to normal synaptic transmission, indicating that a compensatory mechanism is capable of correcting the problem caused by the lack of cdk5. futsch, the Drosophila MAP1B homolog, is also involved in NMJ morphogenesis, and analysis of the NMJ phenotype of the double mutant futschK68; cdk5, indicates that cdk5 is epistatic to futsch in this process. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009 [source] The L1-CAM, Neuroglian, functions in glial cells for Drosophila antennal lobe developmentDEVELOPMENTAL NEUROBIOLOGY, Issue 8 2008Weitao Chen Abstract Although considerable progress has been made in understanding the roles of olfactory receptor neurons (ORNs) and projection neurons (PNs) in Drosophila antennal lobe (AL) development, the roles of glia have remained largely mysterious. Here, we show that during Drosophila metamorphosis, a population of midline glial cells in the brain undergoes extensive cellular remodeling and is closely associated with the collateral branches of ORN axons. These glial cells are required for ORN axons to project across the midline and establish the contralateral wiring in the ALs. We find that Neuroglian (Nrg), the Drosophila homolog of the vertebrate cell adhesion molecule, L1, is expressed and functions in the midline glial cells to regulate their proper development. Loss of Nrg causes the disruption in glial morphology and the agenesis of the antennal commissural tract. Our genetic analysis further demonstrates that the functions of Nrg in the midline glia require its ankyrin-binding motif. We propose that Nrg is an important regulator of glial morphogenesis and axon guidance in AL development. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Seasonal changes in frequency tuning and temporal processing in single neurons in the frog auditory midbrainDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2005Jozien BM Goense Abstract Frogs rely on acoustic signaling to detect, discriminate, and localize mates. In the temperate zone, reproduction occurs in the spring, when frogs emerge from hibernation and engage in acoustically guided behaviors. In response to the species mating call, males typically show evoked vocal responses or other territorial behaviors, and females show phonotactic responses. Because of their strong seasonal behavior, it is possible that the frog auditory system also displays seasonal variation, as evidenced in their vocal control system. This hypothesis was tested in male Northern leopard frogs by evaluating the response characteristics of single neurons in the torus semicircularis (TS; a homolog of the inferior colliculus) to a synthetic mating call at different times of the year. We found that TS neurons displayed a seasonal change in frequency tuning and temporal properties. Frequency tuning shifted from a predominance of TS units sensitive to intermediate frequencies (700,1200 Hz) in the winter, to low frequencies (100,600 Hz) in the summer. In winter and early spring, most TS neurons showed poor, or weak, time locking to the envelope of the amplitude-modulated synthetic call, whereas in late spring and early summer the majority of TS neurons showed robust time-locked responses. These seasonal differences indicate that neural coding by auditory midbrain neurons in the Northern leopard frog is subject to seasonal fluctuation. © 2005 Wiley Periodicals, Inc. J. Neurobiol, 2005 [source] The p73 polymorphisms are not associated with susceptibility to esophageal squamous cell carcinoma in a high incidence region of ChinaDISEASES OF THE ESOPHAGUS, Issue 4 2007H. Ge SUMMARY., P73, a p53 homolog, has some p53-like activities and plays an important role in modulating cell cycle, apoptosis and DNA repair. The two linked polymorphisms in the non-coding region of exon2 of p73 gene, named G4C14-A4T14, may alter translation efficiency of the gene. The transcription of p73 gene is initiated by three promoters, termed P1-P3. There is a single nucleotide substitution (,386G/A) in the P3 promoter region with unknown function. To test the hypothesis that the genetic variations in the exon2 and P3 promoter play a role in the etiology of esophageal squamous cell carcinoma (ESCC), we conducted a population-based case-control study in 348 ESCC patients and 583 healthy controls from a high incidence region of Hebei province, China. The p73 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). The results showed that the family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC (the age, sex and smoking status adjusted OR = 2.02, 95% CI = 1.54,2.67). The overall distribution of the p73 genotype, allelotype and haplotype in cancer patients and controls were not significantly different (all P -values are above 0.05). Stratification analysis by smoking status and family history of UGIC also did not show the significant influence of the polymorphisms on the risk of ESCC development. The results suggested that the p73 exon2 G4C14-A4T14 and P3 promoter ,386G/A polymorphisms might not be used as potential markers to predicate the risk of ESCC development in northern China. [source] Proteomic analysis of liver cancer cells treated with 5-Aza-2,-deoxycytidine (AZA),DRUG DEVELOPMENT RESEARCH, Issue 1 2009Shujun Bai Abstract 5-Aza-2,-deoxycytidine (AZA) is a potent inhibitor of DNA methylation that exhibits anti-tumor activity in a variety of tumor cells via reactivation of tumor suppressor genes. However, few studies have been done on the biological and clinical significance of AZA in human hepatocellular carcinoma. To identify potential genes that may be aberrantly methylated and confer growth advantage to neoplastic cells and to better understand the molecular mechanism(s) underlying AZA anti-tumor activity, a proteomics approach was used to annotate global gene expression changes of HepG2 cell line pre- and post-treatment with AZA. A total of 56 differentially expressed proteins were identified by 2D gel analysis, 48 of which were up-regulated while the remaining 8 were down regulated. Among the identified proteins, eight of these showed marked changed proteins, including seven up-regulated proteins: glutathione S-transferase P, protein DJ-1, peroxiredoxin-2, UMP-CMP kinase, cytochrome c-type heme lyase, enhancer of rudimentary homolog, profilin-1, and one down-regulated protein, heat-shock protein ,,1. The possible implication of these proteins in hepatocarcinogenesis is discussed. We tested two up-regulated proteins, glutathione S-transferase P and peroxiredoxin-2, using RT-PCR and their expression was consistent with the results obtained in the protein level. Both of these genes were methylated when methylation-specific PCR was used against their promoter regions. Following treatment with AZA, the gene promoter regions were found to be unmethylated, concomitant with overexpression of the proteins compared to HepG2 cells without treatment. These data provide useful information in evaluating the therapeutic potential of AZA for the treatment of HCC. Drug Dev Res 69, 2009. © 2009 Wiley-Liss, Inc. [source] Suppression of the mouse double minute 4 gene causes changes in cell cycle control in a human mesothelial cell line responsive to ultraviolet radiation exposureENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2009Melisa Bunderson-Schelvan Abstract The TP53 tumor suppressor gene is the most frequently inactivated gene in human cancer identified to date. However, TP53 mutations are rare in human mesotheliomas, as well as in many other types of cancer, suggesting that aberrant TP53 function may be due to alterations in its regulatory pathways. Mouse double minute 4 (MDM4) has been shown to be a key regulator of TP53 activity, both independently as well as in concert with its structural homolog, Mouse Double Minute 2 (MDM2). The purpose of this study was to characterize the effects of MDM4 suppression on TP53 and other proteins involved in cell cycle control before and after ultraviolet (UV) exposure in MeT5a cells, a nonmalignant human mesothelial line. Short hairpin RNA (shRNA) was used to investigate the impact of MDM4 on TP53 function and cellular transcription. Suppression of MDM4 was confirmed by Western blot. MDM4 suppressed cells were analyzed for cell cycle changes with and without exposure to UV. Changes in cell growth as well as differences in the regulation of direct transcriptional targets of TP53, CDKN1A (cyclin-dependent kinase 1,, p21) and BAX, suggest a shift from cell cycle arrest to apoptosis upon increasing UV exposure. These results demonstrate the importance of MDM4in cell cycle regulation as well as a possible role inthe pathogenesis of mesothelioma-type cancers. Environ. Mol. Mutagen. 2009. © 2009 Wiley-Liss, Inc. [source] Effect of ethoxylate number and alkyl chain length on the pathway and kinetics of linear alcohol ethoxylate biodegradation in activated sludgeENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2004Nina R. Itrich Abstract Batch activated-sludge die-away studies were conducted with various pure homologs to determine the effect of ethoxylate number and alkyl chain length on the kinetics of primary and ultimate biodegradation of linear alcohol ethoxylates. The 14C-(ethoxylate) homologs C14E1, C14E3, C14E6, and C14E9 were used to investigate the effect of ethoxylate number, and 14C-(ethoxylate) homologs C12E6, C14E6, and C16E6 were used to examine the effect of chain length. Activated sludge was dosed with a trace concentration (0.2 ,M) of each homolog, and the disappearance of parent, formation of metabolites, production of 14CO2, and uptake into solids were monitored with time. Ethoxylate number had little effect on the first-order decay rates for primary biodegradation, which ranged from 61 to 78 h,1. However, alkyl chain length had a larger effect, with the C16 chain-length homolog exhibiting a slower rate of parent decay (18 h,1) compared to its corresponding C12 and C14 homologs (61,69 h,1). Ethoxylate number affected the mechanism of biodegradation, with fission of the central ether bond to yield the corresponding fatty alcohol and (poly)ethylene glycol group increasing in dominance with increasing ethoxylate number. Based upon the measured rates of primary biodegradation, removal of parent during activated-sludge treatment was predicted to range between 99.7 and 99.8% for all homologs except C16E6, which had a predicted removal of 98.9%. Based upon the measured rates of ultimate biodegradation, removal of ethoxylate-containing metabolites was predicted to exceed 83% for all homologs. These predictions corresponded closely with previously published removal measurements in laboratory continuous activated-sludge systems and actual treatment plants. [source] The canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2008Frank Abstract The evolutionarily conserved canonical Wnt-,-catenin-T cell factor (TCF)/lymphocyte enhancer binding factor (LEF) signaling pathway regulates key checkpoints in the development of various tissues. Therefore, it is not surprising that a large body of gain-of-function and loss-of-function studies implicate Wnt-,-catenin signaling in lymphopoiesis and hematopoiesis. In contrast, recent papers have reported that Mx-Cre-mediated conditional deletion of ,-catenin and/or its homolog ,-catenin (plakoglobin) did not impair hematopoiesis or lymphopoiesis. However, these studies also report that TCF reporter activity remains active in ,-catenin- and ,-catenin-deficient hematopoietic stem cells and all cells derived from these precursors, indicating that the canonical Wnt signaling pathway was not abrogated. Therefore, these studies in fact show that the canonical Wnt signaling pathway is important in hematopoiesis and lymphopoiesis, even though the molecular basis for the induction of the reporter activity is currently unknown. In this perspective, we provide a broad background to the field with a discussion of the available data and create a framework within which the available and future studies may be evaluated. [source] Both CD133+ and CD133, medulloblastoma cell lines express ligands for triggering NK receptors and are susceptible to NK-mediated cytotoxicityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 11 2007Roberta Castriconi Abstract Adoptive cellular immunotherapy has been proposed as an additional treatment of medulloblastoma, an intracranial tumor characterized by a particularly poor prognosis. However, little is known on the ability of the immune system to effectively attack this tumor. In this study, we show that activated human NK cells efficiently kill medulloblastoma cell lines in vitro. NK-mediated killing involved different activating receptors (including NKp46, NKp30, DNAM-1 and NKG2D) and correlated with the presence of their specific ligands on tumor cells. In contrast, the absence of major adhesion interactions, such as LFA-1/ICAM did not impair the NK-mediated cytotoxicity. Medulloblastoma expressed a number of tumor-associated molecules including CD146 and CD133, considered a marker for cancer stem cells. Remarkably, both CD133-positive and CD133-negative cell lines were susceptible to lysis. Tumor cells also expressed molecules that are currently used as diagnostic tools for neuroblastoma cell identification. In particular, B7 homolog 3 (B7-H3) was expressed by all the medulloblastoma cell lines analyzed, while the presence of GD2 and NB84 was restricted to given cell lines and/or marked a defined tumor cell subset. [source] Specific ICAM-3 grabbing nonintegrin-related 1 (SIGNR1) expressed by marginal zone macrophages is essential for defense against pulmonary Streptococcuspneumoniae infectionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2005Estella Abstract The dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) homolog, SIGN-related 1 (SIGNR1) is a pathogen receptor expressed by splenic marginal zone and peritoneal macrophages, and is essential for clearance of Streptococcus pneumoniae by phagocytosis after intraperitoneal infection. Here, we identified an important in vivo function for SIGNR1 in S.pneumonia infection induced via its natural entrance route. Upon intranasal infection with S. pneumoniae, SIGNR1-deficient mice did not clear bacteria from lung and blood, and displayed severely enhanced inflammatory parameters compared to the wild-type mice. However, SIGNR1 is not expressed by alveolar macrophages, suggesting that another mechanism than a decrease in phagocytosis is responsible for this difference. Natural anti-phosphorylcholine IgM produced by marginal zone B cells is essential for protection against infection with S. pneumoniae. Strikingly, during infection, SIGNR1-deficient mice failed to produce a rapid anti-phosphorylcholine IgM response. Marginal zone macrophages have been suggested to capture antigens for presentation to marginal zone B cells. We demonstrate that marginal zone macrophages from SIGNR1-deficient mice in contrast to wild-type mice are not able to capture pneumococci from blood, suggesting that SIGNR1 on marginal zone macrophages captures S. pneumoniae for antigen presentation to and activation of marginal zone B cells, resulting in an anti-phosphorylcholine IgM response. [source] Expression of lymphocyte activation gene 3 (LAG-3) on B cells is induced by T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2005Malgorzata Kisielow Abstract Lymphocyte activation gene 3 (LAG-3/CD223) is a CD4 homolog known to be selectively expressed in activated T and NK cells. It is thought to have a negative regulatory function in T cells. With the help of new monoclonal antibodies against mouse LAG-3, we show that LAG-3 surface expression is not limited to activated T and NK cells but is also found on activated B cells. Induction of B cell surface expression is T cell dependent and mediated by a soluble factor. The majority of LAG-3 on B cell surface is endogenously produced, even though soluble LAG-3 is present in the culture supernatants and can be passively absorbed. As B cells express LAG-3 in a T cell dependent manner and not when activated by Toll-like-receptor agonists alone, we propose LAG-3 as a new marker of T cell induced B cell activation. [source] Interaction of a novel mitochondrial protein, 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1), with the amyloid precursor protein familyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2010Hemachand Tummala Abstract Amyloid precursor protein (APP) and its paralogs, amyloid precursor-like protein-1 and amyloid precursor-like protein-2, appear to have redundant but essential role(s) during development. To gain insights into the physiological and possibly pathophysiological functions of APP, we used a functional proteomic approach to identify proteins that interact with the highly conserved C-terminal region of APP family proteins. Previously, we characterized an interaction between APP and ubiquitous mitochondrial creatine kinase. Here, we describe an interaction between APP and a novel protein, 4-nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1). The interaction between APP and NIPSNAP1 was confirmed both in transiently transfected COS7 cells and in the mouse brain, where NIPSNAP1 is expressed at a high level. We demonstrate that NIPSNAP1 is targeted to the mitochondria via its N-terminal targeting sequence, and interacts with mitochondrial chaperone translocase of the outer membrane 22. Mitochondrial localization of NIPSNAP1 appears to be critical for its interaction with APP, and overexpression of APP appeared to disrupt NIPSNAP1 mitochondrial localization. Moreover, APP overexpression resulted in downregulation of NIPSNAP1 levels in cultured cells. Our data suggest that APP may affect mitochondrial function through a direct interaction with NIPSNAP1 as well as with other mitochondrial proteins. [source] Adenylyl cyclase encoded by AC78C participates in sugar perception in Drosophila melanogasterEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2008Kohei Ueno Abstract In gustatory receptor neurons (GRNs) in Drosophila melanogaster, Gr5a and one of the Gr64s encode sugar receptors with seven transmembrane domains. Previously, we have shown that the responses to various sugars are depressed in DGs, mutant flies (Ueno et al., 2006). Because DGs, is a homolog of Gs, we hypothesized that the sugar receptors are coupled to adenylyl cyclase (AC) in Drosophila. The aim of this study was to identify the AC that participates in sugar perception. Here, we found that an AC inhibitor, MDL-12330A, depressed the response in GRNs to trehalose as well as sucrose; that an AC gene, AC78C, was expressed in the sugar-sensitive GRNs; that RNAi against AC78C depressed the electrical response in GRNs to sucrose; and that the sugar response in GRNs, as well as sugar intake in a behavioral assay in an AC78C mutant, was depressed at low sugar concentrations. We conclude that AC78C, via cAMP, participates in the sugar-taste signaling pathway at the low concentration range. [source] Laser capture microdissection and microarray analysis of dividing neural progenitor cells from the adult rat hippocampusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2007Ulf Gurok Abstract Neural progenitor cells reside in the hippocampus of adult rodents and humans and generate granule neurons throughout life. Knowledge about the molecular processes regulating these neurogenic cells is fragmentary. In order to identify genes with a role in the proliferation of adult neural progenitor cells, a protocol was elaborated to enable the staining and isolation of such cells under RNA-preserving conditions with a combination of immunohistochemistry and laser capture microdissection. We increased proliferation of neural progenitor cells by electroconvulsive treatment, one of the most effective antidepressant treatments, and isolated Ki-67-positive cells using this new protocol. RNA amplification via in vitro transcription and subsequent microarray analysis revealed over 100 genes that were differentially expressed in neural progenitor cells due to electroconvulsive treatment compared to untreated control animals. Some of these genes have already been implicated in the functioning of neural progenitor cells or have been induced by electroconvulsive treatment; these include brain-derived neurotrophic factor (Bdnf), PDZ-binding kinase (Pbk) and abnormal spindle-like microcephaly-associated (Aspm). In addition, genes were identified for which no role in the proliferation of neurogenic progenitors has been described so far, such as enhancer of zeste homolog 2 (Ezh2). [source] | |||||||||||||||||||||||||||||||||||||||||||