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Novel Member (novel + member)

Distribution by Scientific Domains

Medical Sciences	40%
Life Sciences	40%
Chemistry	16%

Distribution within Medical Sciences

Oncology & Radiotherapy	25%
Pathology	15%

Selected Abstracts

Novel member of the mouse desmoglein gene family: Dsg1-,

EXPERIMENTAL DERMATOLOGY, Issue 1 2003
L. Pulkkinen
Abstract: Desmosomes are major intercellular adhesion junctions that provide stable cell,cell contacts and mechanical strength to epithelial tissues by anchoring cytokeratin intermediate filaments of adjacent cells. Desmogleins (Dsg) are transmembrane core components of the desmosomes, and belong to the cadherin supergene family of calcium-dependent adhesion molecules. Currently, there are three known isoforms of Dsgs (Dsg1, Dsg2, and Dsg3), encoded by distinct genes that are differentially expressed to determine their tissue specificity and differentiation state of epithelial cells. In this study, we cloned a novel mouse desmoglein gene sharing high homology to both mouse and human Dsg1. We propose to designate the previously published mouse Dsg1 gene as Dsg1- , and the new gene as Dsg1-,. Analysis of intron/exon organization of the Dsg1-, and Dsg1-, genes revealed significant conservation. The full-length mouse Dsg1-, cDNA contains an open reading frame of 3180 bp encoding a precursor protein of 1060 amino acids. Dsg1-, protein shares 94% and 76% identity with mouse Dsg1-, and human DSG1, respectively. RT-PCR using a multitissue cDNA panel demonstrated that while Dsg1-, mRNA was expressed in 15- to 17-day-old embryos and adult spleen and testis, Dsg1-, mRNA was detected in 17-day-old embryos only. To assess subcellular localization, a FLAG-tagged expression construct of Dsg1-, was transiently expressed in epithelial HaCaT cells. Dsg1-,-FLAG was found at the cell,cell border and was recognized by the anti-Dsg1/Dsg2 antibody DG3.10. In summary, we have cloned and characterized a novel member of the mouse desmoglein gene family, Dsg1-,. [source]

Neuronal leucine-rich repeat 6 (XlNLRR-6) is required for late lens and retina development in Xenopus laevis

DEVELOPMENTAL DYNAMICS, Issue 4 2006
Adam D. Wolfe
Abstract Leucine-rich repeat proteins expressed in the developing vertebrate nervous system comprise a complex, multifamily group, and little is known of their developmental function in vivo. We have identified a novel member of this group in Xenopus laevis, XlNLRR-6, and through sequence and phylogenetic analysis, have placed it within a defined family of vertebrate neuronal leucine-rich repeat proteins (NLRR). XlNLRR-6 is expressed in the developing nervous system and tissues of the eye beginning at the neural plate stage, and expression continues throughout embryonic and larval development. Using antisense morpholino oligonucleotide (MO) -mediated knockdown of XlNLRR-6, we demonstrate that this protein is critical for development of the lens, retina, and cornea. Reciprocal transplantation of presumptive lens ectoderm between MO-treated and untreated embryos demonstrate that XlNLRR-6 plays autonomous roles in the development of both the lens and retina. These findings represent the first in vivo functional analysis of an NLRR family protein and establish a role for this protein during late differentiation of tissues in the developing eye. Developmental Dynamics 235:1027,1041, 2006. © 2006 Wiley-Liss, Inc. [source]

Novel metalloprotease,disintegrin, meltrin , (ADAM35), expressed in epithelial tissues during chick embryogenesis

DEVELOPMENTAL DYNAMICS, Issue 3 2004
Mitsuko Watabe-Uchida
Abstract Members of the ADAM (adisintegrin and metalloprotease) family are involved in fertilization, morphogenesis, and pathogenesis. Their metalloprotease domains mediate limited proteolysis, including ectodomain shedding of membrane-anchored growth factors and intercellular-signaling proteins, and their disintegrin domains play regulatory roles in cell adhesion and migration. In screening for cDNAs encoding chicken ADAM proteins expressed during muscle development, we identified Meltrin , as a novel member of this family. To elucidate its functions, we investigated its expression during development by using antibodies raised against its protease domain. In the somites, Meltrin , protein was specifically expressed in the myotomal cells, which delaminate from the dermomyotome to form epithelial sheets. It was also found in the surface ectoderm, lens placodes, otic vesicles, and the gut epithelia. Basolateral localization of Meltrin , in these epithelial cells suggests its unique roles in the organization of the epithelial tissues and development of the sensory organs and the gut. Developmental Dynamics 230:557,568, 2004. © 2004 Wiley-Liss, Inc. [source]

An SNF2 factor involved in mammalian development and cellular proliferation

DEVELOPMENTAL DYNAMICS, Issue 1 2001
Eric H. Raabe
Abstract Members of the SNF2 (Sucrose Non-Fermenter) family of chromatin-remodeling proteins function in processes ranging from DNA repair to transcription to methylation. Using differential display, we recently identified a novel member of the SNF2 family that is highly expressed at the mRNA level in proliferating cells and is down-regulated during apoptosis. We have named this gene PASG (Proliferation-Associated SNF2-like Gene). Northern blot analysis of adult mouse tissues shows PASG to be highly expressed in proliferating organs such as thymus, bone marrow, and testis and absent from nonproliferative tissues such as brain and heart. In situ hybridization analysis of mouse embryos shows that PASG is differentially expressed during development, with highest expression in developing face, limbs, skeletal muscle, heart, and tail. In vitro, PASG expression correlates with a shift from a quiescent to a proliferative state. Mice null for PASG (also known as LSH or Hells) are reported to die perinatally, although the mechanism for lethality is unclear (Geiman and Muegge, 2000). To test the hypothesis that PASG functions in cell proliferation, we compared 5-bromodeoxyuridine (BrdU) incorporation in C33A cells transiently transfected with PASG versus empty vector and found that PASG transfected cells showed a significant decrease in the amount of BrdU incorporation. These findings suggest that PASG plays a role in cell proliferation and may function in the development of multiple cell lineages during murine embryogenesis. © 2001 Wiley-Liss, Inc. [source]

A novel approach to tag and identify geranylgeranylated proteins

ELECTROPHORESIS, Issue 20 2009
Lai N. Chan
Abstract A recently developed proteomic strategy, the "GG-azide"-labeling approach, is described for the detection and proteomic analysis of geranylgeranylated proteins. This approach involves metabolic incorporation of a synthetic azido-geranylgeranyl analog and chemoselective derivatization of azido-geranylgeranyl-modified proteins by the "click" chemistry, using a tetramethylrhodamine-alkyne. The resulting conjugated proteins can be separated by 1-D or 2-D and pH fractionation, and detected by fluorescence imaging. This method is compatible with downstream LC-MS/MS analysis. Proteomic analysis of conjugated proteins by this approach identified several known geranylgeranylated proteins as well as Rap2c, a novel member of the Ras family. Furthermore, prenylation of progerin in mouse embryonic fibroblast cells was examined using this approach, demonstrating that this strategy can be used to study prenylation of specific proteins. The "GG-azide"-labeling approach provides a new tool for the detection and proteomic analysis of geranylgeranylated proteins, and it can readily be extended to other post-translational modifications. [source]

The DC-SIGN family member LSECtin is a novel ligand of CD44 on activated T cells

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2010
Li Tang
LSECtin, a novel member of the C-type lectin DC-SIGN family, not only acts as an attachment factor for pathogens, but also recognizes "endogenous" activated T cells. The endogenous ligands of LSECtin, however, have remained unclear. In this study, we identified CD44 on Jurkat T cells as a candidate ligand of LSECtin, and confirmed the specific interaction between LSECtin and CD44. Moreover, we showed that LSECtin selectively bound CD44s, CD44v4 and CD44v8-10 by screening a series of typical CD44 isoforms. By deletion of the carbohydrate-recognition domain region and mutation of crucial amino acids involved in carbohydrate-recognition of LSECtin and by inhibition of the N-linked glycosylation of CD44, we further demonstrated that the interaction between CD44 and LSECtin is dependent on protein-glycan recognition. Our findings indicate that CD44 is the first identified endogenous ligand of LSECtin, and similarly, that LSECtin is a novel ligand of CD44. These findings provide important new perspectives on the biology of both LSECtin and CD44 in the immune system. [source]

Genomic annotation and transcriptome analysis of the zebrafish (Danio rerio) hox complex with description of a novel member, hoxb13a

EVOLUTION AND DEVELOPMENT, Issue 5 2005
M. Corredor-Adámez
Summary The zebrafish (Danio rerio) is an important model in evolutionary developmental biology, and its study is being revolutionized by the zebrafish genome project. Sequencing is at an advanced stage, but annotation is largely the result of in silico analyses. We have performed genomic annotation, comparative genomics, and transcriptional analysis using microarrays of the hox homeobox-containing transcription factors. These genes have important roles in specifying the body plan. Candidate sequences were located in version Zv4 of the Ensembl genome database by TBLASTN searching with Danio and other vertebrate published Hox protein sequences. Homologies were confirmed by alignment with reference sequences, and by the relative position of genes along each cluster. RT-PCR using adult Tübingen cDNA was used to confirm annotations, to check the genomic sequence and to confirm expression in vivo. Our RT-PCR and microarray data show that all 49 hox genes are expressed in adult zebrafish. Significant expression for all known hox genes could be detected in our microarray analysis. We also find significant expression of hox8 paralogs and hoxb7a in the anti-sense direction. A novel gene, D. rerio hoxb13a, was identified, and a preliminary characterization by in situ hybridization showed expression at 24 hpf at the tip of the developing tail. We are currently characterizing this gene at the functional level. We argue that the oligo design for microarrays can be greatly enhanced by the availability of genomic sequences. [source]

Molecular genetics of Xeroderma pigmentosum variant

EXPERIMENTAL DERMATOLOGY, Issue 5 2003
Alexei Gratchev
Skin abnormalities result from an inability to repair UV-damaged DNA because of defects in the nucleotide excision repair (NER) machinery. Xeroderma pigmentosum is genetically heterogeneous and is classified into seven complementation groups (XPA-XPG) that correspond to genetic alterations in one of seven genes involved in NER. The variant type of XP (XPV), first described in 1970 by Ernst G. Jung as ,pigmented xerodermoid', is caused by defects in the post replication repair machinery while NER is not impaired. Identification of the XPV gene was only achieved in 1999 by biochemical purification and sequencing of a protein from HeLa cell extracts complementing the PRR defect in XPV cells. The XPV protein, polymerase (pol),, represents a novel member of the Y family of bypass DNA polymerases that facilitate DNA translesion synthesis. The major function of pol, is to allow DNA translesion synthesis of UV-induced TT-dimers in an error-free manner; it also possesses the capability to bypass other DNA lesions in an error-prone manner. Xeroderma pigmentosum V is caused by molecular alterations in the POLH gene, located on chromosome 6p21.1,6p12. Affected individuals are homozygous or compound heterozygous for a spectrum of genetic lesions, including nonsense mutations, deletions or insertions, confirming the autosomal recessive nature of the condition. Identification of POLH as the XPV gene provides an important instrument for improving molecular diagnostics in XPV families. [source]

Novel member of the mouse desmoglein gene family: Dsg1-,

cDNA cloning and characterization of a novel calmodulin-like protein from pearl oyster Pinctada fucata

FEBS JOURNAL, Issue 19 2005
Shuo Li
Calcium metabolism in oysters is a very complicated and highly controlled physiological and biochemical process. However, the regulation of calcium metabolism in oyster is poorly understood. Our previous study showed that calmodulin (CaM) seemed to play a regulatory role in the process of oyster calcium metabolism. In this study, a full-length cDNA encoding a novel calmodulin-like protein (CaLP) with a long C-terminal sequence was identified from pearl oyster Pinctada fucata, expressed in Escherichia coli and characterized in vitro. The oyster CaLP mRNA was expressed in all tissues tested, with the highest levels in the mantle that is a key organ involved in calcium secretion. In situ hybridization analysis reveals that CaLP mRNA is expressed strongly in the outer and inner epithelial cells of the inner fold, the outer epithelial cells of the middle fold, and the dorsal region of the mantle. The oyster CaLP protein, with four putative Ca2+ -binding domains, is highly heat-stable and has a potentially high affinity for calcium. CaLP also displays typical Ca2+ -dependent electrophoretic shift, Ca2+ -binding activity and significant Ca2+ -induced conformational changes. Ca2+ -dependent affinity chromatography analysis demonstrated that oyster CaLP was able to interact with some different target proteins from those of oyster CaM in the mantle and the gill. In summary, our results have demonstrated that the oyster CaLP is a novel member of the CaM superfamily, and suggest that the oyster CaLP protein might play a different role from CaM in the regulation of oyster calcium metabolism. [source]

Potential active-site residues in polyneuridine aldehyde esterase, a central enzyme of indole alkaloid biosynthesis, by modelling and site-directed mutagenesis

FEBS JOURNAL, Issue 12 2002
Emine Mattern-Dogru
In the biosynthesis of the antiarrhythmic alkaloid ajmaline, polyneuridine aldehyde esterase (PNAE) catalyses a central reaction by transforming polyneuridine aldehyde into epi-vellosimine, which is the immediate precursor for the synthesis of the ajmalane skeleton. The PNAE cDNA was previously heterologously expressed in E. coli. Sequence alignments indicated that PNAE has a 43% identity to a hydroxynitrile lyase from Hevea brasiliensis, which is a member of the ,/, hydrolase superfamily. The catalytic triad, which is typical for this family, is conserved. By site-directed mutagenesis, the members of the catalytic triad were identified. For further detection of the active residues, a model of PNAE was constructed based on the X-ray crystallographic structure of hydroxynitrile lyase. The potential active site residues were selected on this model, and were mutated in order to better understand the relationship of PNAE with the ,/, hydrolases, and as well its mechanism of action. The results showed that PNAE is a novel member of the ,/, hydrolase enzyme superfamily. [source]

Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): Upregulated colonic IL-17F expression in active Crohn's disease and analysis of the IL17F p.His161Arg polymorphism in IBD

INFLAMMATORY BOWEL DISEASES, Issue 4 2008
Julia Seiderer MD
Abstract Background: Interleukin (IL)-17F, produced in IL-23R-expressing Th17 cells, is a novel member of the IL-17 cytokine family. Given the association of IL23R with inflammatory bowel disease (IBD), we characterized the role of IL-17F in IBD including its intestinal gene expression and the effect of the IL17F p.His161Arg polymorphism on disease susceptibility and phenotype of Crohn's disease (CD) and ulcerative colitis (UC). In addition, we analyzed the IL17F p.His161Arg polymorphism for potential epistasis with IL23R and NOD2/CARD15 variants. Methods: Intestinal IL-17F mRNA expression was measured by quantitative polymerase chain reaction (PCR). Genomic DNA from 1682 individuals (CD: n = 499; UC: n = 216; controls: n = 967) was analyzed for the presence of the IL17F p.His161Arg polymorphism, the 3 NOD2 variants, p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008, and 10 CD-associated IL23R variants. Results: Intestinal IL-17F mRNA expression was 4.4-fold increased in inflamed colonic lesions compared to uninflamed biopsies in CD (P = 0.016) but not in UC. However, the mean intestinal IL-17F mRNA expression was higher in UC than in CD (P < 0.0001). The IL17F p.His161Arg substitution was observed with similar frequencies in IBD patients and controls and was not associated with a certain disease phenotype, but weakly associated with a low body mass index (BMI; P = 0.009) and an earlier age of disease onset (P = 0.039) in UC. There was no evidence for epistasis between the IL17F p.His161Arg polymorphism and IBD-associated single nucleotide polymorphisms within the IL23R gene. Conclusions: Intestinal IL17F gene expression is increased in active CD. The IL17F p.His161Arg polymorphism is not associated with IBD susceptibility and has no epistatic interaction with CD-associated IL23R variants. (Inclamm Bowel Dis 2007) [source]

PARP-3 associates with polycomb group bodies and with components of the DNA damage repair machinery

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2007
M. Rouleau
Abstract Poly(ADP-ribose) polymerase 3 (PARP-3) is a novel member of the PARP family of enzymes that synthesize poly(ADP-ribose) on themselves and other acceptor proteins. Very little is known about this PARP, which is closely related to PARP-1 and PARP-2. By sequence analysis, we find that PARP-3 may be expressed in two isoforms which we studied in more detail to gain insight into their possible functions. We find that both PARP-3 isoforms, transiently expressed as GFP or FLAG fusions, are nuclear. Detection of endogenous PARP-3 with a specific antibody also shows a widespread nuclear distribution, appearing in numerous small foci and a small number of larger foci. Through co-localization experiments and immunoprecipitations, the larger nuclear foci were identified as Polycomb group bodies (PcG bodies) and we found that PARP-3 is part of Polycomb group protein complexes. Furthermore, using a proteomics approach, we determined that both PARP-3 isoforms are part of complexes comprising DNA-PKcs, PARP-1, DNA ligase III, DNA ligase IV, Ku70, and Ku80. Our findings suggest that PARP-3 is a nuclear protein involved in transcriptional silencing and in the cellular response to DNA damage. J. Cell. Biochem. 100: 385,401, 2007. © 2006 Wiley-Liss, Inc. [source]

Novel putative nonprotein-coding RNA gene from 11q14 displays decreased expression in brains of patients with schizophrenia

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2003
Oxana O. Polesskaya
Abstract A modified method of differential display was employed to identify a novel gene (named PSZA11q14), the expression of which was reduced in brains from patients with schizophrenia. Decreased expression of PSZA11q14 was identified initially in Brodmann's area (BA) 21 from a small group of patients with schizophrenia (n = 4) and normal controls (n = 6) and was confirmed subsequently using independent RT-PCR assay in BA 21, 22, and 9, and in hippocampus from a larger group of patients with schizophrenia (n = 36) and controls (n = 35). PSZA11q14 is located on chromosome 11q14, an area shown previously to co-segregate with schizophrenia and related disorders in several families. Decreased expression of PSZA11q14 in patients with schizophrenia and its location on 11q14 provide converging lines of evidence indicating that PSZA11q14 may be involved in at least some cases of schizophrenia. PSZA11q14 shows no significant homology with any known gene. It has no introns and produces two RNA transcripts of ,4.5 and ,7.0 kb. The largest open reading frame (ORF) in the PSZA11q14 transcripts may potentially encode for a short polypeptide of 71 amino acids. High frequency of rare codons, the short size of this ORF, and low homology with mouse sequences, however, indicate that PSZA11q14 may instead represent a novel member of a family of nonprotein-coding RNA genes that are not translated and that function at the RNA level. PSZA11q14 is located within the first intron of the DLG-2 gene and transcribed in the opposite direction to DLG-2. These results suggest that PSZA11q14 may be considered a candidate gene for schizophrenia acting as an antisense regulator of DLG-2, which controls assembling functional N -methyl- D -aspartate (NMDA) receptors. © 2003 Wiley-Liss, Inc. [source]

A novel member of the glycosyltransferase family, ,3Gn-T2, highly downregulated in invasive human bladder transitional cell carcinomas

MOLECULAR CARCINOGENESIS, Issue 2 2001
Irina Gromova
Abstract Differential display reverse transcription (DDRT),polymerase chain reaction (PCR) was used to compare the transcriptomes of invasive and noninvasive fresh human bladder transitional cell carcinomas. A differentially expressed novel gene sharing structural similarity with the human ,3-galactosyltransferase family, ,-1,3- N -acetylglucosaminyltransferase-T2 (,3Gn-T2), was identified. The full-length ,3Gn-T2 cDNA, containing a complete open reading frame of 1193 bp, was cloned and sequenced. ,3Gn-T2 exhibited 29,41% homology to the multigene ,3-galactosyltransferase family. Expression of the full-length ,3Gn-T2 cDNA in an in vitro coupled transcription/translation assay yielded a primary translation product with an apparent Mr of 46 kDa, which is in agreement with the predicted 397-amino-acid protein encoded by ,3Gn-T2. Multiple peptide alignment showed several sequence motifs corresponding to putative catalytic domains that are conserved throughout all members of the ,3-galactosyltransferase family, namely, a type II transmembrane domain, a conserved DxD motif, an N -glycosylation site, and five conserved cysteins. By RT-PCR strong downregulation of ,3Gn-T2 expression was noted in invasive human bladder transitional cell carcinomas (16 fresh biopsy samples: grade III, T2,T4) compared with their noninvasive counterparts (15 fresh biopsies: grade II, Ta), suggesting that ,3Gn-T2 may be involved in cancer progression. © 2001 Wiley-Liss, Inc. [source]

A novel NO-responding regulator controls the reduction of nitric oxide in Ralstonia eutropha

MOLECULAR MICROBIOLOGY, Issue 3 2000
Anne Pohlmann
Ralstonia eutropha H16 mediates the reduction of nitric oxide (NO) to nitrous oxide (N2O) with two isofunctional single component membrane-bound NO reductases (NorB1 and NorB2). This reaction is integrated into the denitrification pathway that involves the successive reduction of nitrate to dinitrogen. The norB1 gene is co-transcribed with norA1 from a ,54 (RpoN)-dependent promoter, located upstream of norA1. With the aid of norA1,,lacZ transcriptional fusions and the generation of regulatory mutants, it was shown that norB1 gene transcription requires a functional rpoN gene and the regulator NorR, a novel member of the NtrC family of response regulators. The regulator gene maps adjacent to norAB, is divergently transcribed and present in two copies on the megaplasmid pHG1 (norR1) and the chromosome (norR2). Transcription activation by NorR responds to the availability of NO. A nitrite reductase-deficient mutant that is incapable of producing NO endogenously, showed a 70% decrease of norA1 expression. Addition of the NO-donating agent sodium nitroprusside caused induction of norA1,,lacZ transcription. Truncation of the N-terminal receiver domain of NorR1 interrupted the NO signal transduction and led to a constitutive expression of norA1,,lacZ. The results indicate that NorR controls the reductive conversion of NO in R. eutropha. This reaction is not strictly co-ordinated on the regulatory level with the other nitrogen oxide-reducing steps of the denitrification chain that are independent of NorR. [source]

Malignant craniopharyngioma; case report and review of the literature

NEUROPATHOLOGY, Issue 5 2009
Atthaporn Boongird
A case of malignant craniopharyngioma in a 46-year-old woman presenting clinically with visual disturbance and bifrontal headache is reported. Histopathologic examination of the suprasellar mass showed a lesion characterized by nests of epithelial cells with a basaloid appearance, round-to-oval nuclei, moderate pleomorphism, hyperchromasia, increased nuclear cytoplastic ratio and high mitotic activity. Immunohistochemically, the tumor cells were positive for Ki-67 (44.3%), p53 (98%), and p63 (100%), but negative for estrogen and progesterone receptors. Clinical and pathologic features with a brief review of the relevant literature for malignant craniopharyngioma as a novel member of tumors of the suprasellar region, is discussed. [source]

p73: Structure and function

PATHOLOGY INTERNATIONAL, Issue 8 2000
Shingo Ichimiya
Alteration of the p53 tumor suppressor gene is a common, if not general, observation in human malignant tumors. p73 Is a novel member of the p53 family at chromosome 1p36.3, at which locus frequent defects are seen in many tumors including neuroblastoma. Besides structural similarities, the fact that p73 functions in the regulation of the cell cycle and apoptosis promotes the expansion of the research field concerning p53-associated tumor progression. In this paper, we review the structure and function of p73 as well as the mutational status in various human tumors. In addition, possibilities for new therapeutic applications with p73 for cancer cell control are discussed. [source]

Large subunit rDNA and rbcL gene sequence data place Petrohua bernabei gen. et sp. nov. in the Batrachospermales (Rhodophyta), but do not provide further resolution among taxa in this order

PHYCOLOGICAL RESEARCH, Issue 2 2007
Morgan L. Vis
SUMMARY The phylogenetic relationship among 12 previously described batrachospermalean taxa and a novel member of the order were investigated using the LSU and rbcL genes separately and in combination. The primary goal of this research was to establish the phylogenetic placement of a previously undescribed freshwater red alga from Chile. The results showed that the new entity with pseudoparenchymatous tube morphology is a member of the Batrachospermales and Petrohua bernabei gen. et sp. nov. is described herein. This is the first record to our knowledge of a Lemanea -like alga from Chile. It would appear that this thallus construction has evolved at least three times in the Batrachospermales and that the switch from a Batrachospermum -like construction to a pseudoparenchymatous construction may be a repeated adaptive response to turbulent waterfall habitats. In addition to providing information about a new freshwater red alga, this study sought to determine whether combining the data from two genes would produce a more robust phylogeny, particularly for intermediate nodes, to resolve familial relationships within the order. As with previous analyses, the Batrachospermales was resolved as a clade and support was high for relationships resolved among relatively recent nodes. Unfortunately, combining the LSU and rbcL data did not have the desired effect of more fully resolving intermediate nodes among the Batrachospermales. [source]

Small G-protein RhoE is underexpressed in prostate cancer and induces cell cycle arrest and apoptosis

THE PROSTATE, Issue 4 2005
Jasmin Bektic
Abstract BACKGROUND RhoE/Rnd3, a recently described novel member of the Rho GTPases family, was discussed as a possible antagonist of the RhoA protein that stimulates cell cycle progression and is overexpressed and/or overactivated in prostate cancer. We investigated the expression of RhoE and its role in cell cycle regulation and apoptosis in the human prostate. METHODS RhoE expression in cell lines and tissue specimens was assessed by immunoblot analysis, real-time PCR (RT-PCR), and immunohistochemistry. To elucidate RhoE effects on the prostate, RhoE was cloned and overexpressed in DU-145 prostate cancer. Cell cycle modulation and apoptosis was investigated by immunoblot and FACS analysis. RESULTS Immunoblot analysis showed a strong RhoE signal in both, benign epithelial and stromal cells. In contrast, almost no protein was detected in various prostate cancer cells. On RT-PCR and microarray analysis, RhoE mRNA expression was significantly reduced in malignant tissue when compared to benign samples. RhoE immunostaining was strong in benign tissue, especially in prostate epithelial cells, whereas it was minimal or absent in malignant tissue. Forced RhoE overexpression in a prostate cancer cell line inhibits the expression of two proteins essential for G2/M transition, namely CDC2 and cyclin B1, and induces G2/M arrest. In addition, apoptotic cell death as measured by a cleavage product of caspase 3 is significantly increased in RhoE-overexpressing cells. CONCLUSION In conclusion, our findings suggest RhoE as a tumor suppressor gene that is downregulatated early in the development of prostate cancer. © 2005 Wiley-Liss, Inc. [source]

Isolation, sequence, and chromosomal localisation of the human I,BR gene (NFKBIL2)

ANNALS OF HUMAN GENETICS, Issue 1 2000
D. A. M. NORMAN
The inhibitors of NF-,B (I,Bs) play an important role in the regulation of the NF-,B pathway. I,BR (for I,B -Related) is proposed to be a novel member of this family. We report the cloning and characterization of the region of the human gene encoding the previously reported mRNA. This region contains 13 exons, spread over 6550 bp of genomic sequence. The coding sequence is only weakly similar to other I,Bs and the exons display a more complicated structure than has been found in other members of the I,B gene family. Moreover, the positions of intron-exon junctions are different from those found in other I,B genes, even within the otherwise conserved ankyrin-like repeat region, suggesting that the I,BR gene is not a member of this extended gene family. We report a revised mRNA and protein sequence for I,BR, which predicts that the protein is larger than originally described. We also report the chromosomal localisation of the human I,BR gene (approved gene symbol NFKBIL2) to 8q24.3 using PCR-based somatic cell hybrid panel analysis and fluorescence in situ hybridization (FISH) mapping. [source]

Structure of recombinant human cyclophilin J, a novel member of the cyclophilin family

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2005
Li-Li Huang
Cyclophilins (CyPs) are a large class of highly conserved ubiquitous peptidyl-prolyl cis,trans isomerases. CyPs have also been identified as being a specific receptor for the immunosuppressive drug cyclosporin A and are involved in a variety of biological functions. CyPJ is a novel member of the CyP family and human CyPJ (hCyPJ) is the protein encoded by a cyclophilin-like gene from human foetal brain, which shows 50% sequence identity to human cyclophilin A (hCyPA). Recombinant hCyPJ was expressed in Escherichia coli and purified. The three-dimensional structure of hCyPJ has been determined by molecular replacement using the hCyPA structure as the search model and has been refined at 2.6,Å resolution. The hCyPJ molecule contains four helices and one ,-barrel composed of eight antiparallel ,-strands. The overall secondary and tertiary structures of hCyPJ are similar to those of hCyPA, but hCyPJ contains an additional disulfide bridge and four segments with conformations that are strikingly different from those of hCyPA. His43 and Gln52 of hCyPJ are expected to be the active sites based on sequence alignment with hCyPA. The hCyPJ structure shows a conserved water molecule close to His43 and Gln52 which appears to support the solvent-assisted mechanism. [source]

Purification, crystallization and preliminary X-ray diffraction of human S100A15

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 5 2006
Karen M. Boeshans
Human S100A15 is a novel member of the S100 family of EF-hand calcium-binding proteins and was recently identified in psoriasis, where it is significantly upregulated in lesional skin. The protein is implicated as an effector in calcium-mediated signal transduction pathways. Although its biological function is unclear, the association of the 11.2,kDa S100A15 with psoriasis suggests that it contributes to the pathogenesis of the disease and could provide a molecular target for therapy. To provide insight into the function of S100A15, the protein was crystallized to visualize its structure and to further the understanding of how the many similar calcium-binding mediator proteins in the cell distinguish their cognate target molecules. The S100A15 protein has been cloned, expressed and purified to homogeneity and produced two crystal forms. Crystals of form I are triclinic, with unit-cell parameters a = 33.5, b = 44.3, c = 44.8,Å, , = 71.2, , = 68.1, , = 67.8° and an estimated two molecules in the asymmetric unit, and diffract to 1.7,Å resolution. Crystals of form II are monoclinic, with unit-cell parameters a = 82.1, b = 33.6, c = 52.2,Å, , = 128.2° and an estimated one molecule in the asymmetric unit, and diffract to 2.0,Å resolution. This structural analysis of the human S100A15 will further aid in the phylogenic comparison between the other members of the S100 protein family, especially the highly homologous paralog S100A7. [source]

Nitroxide tempo, a small molecule, induces apoptosis in prostate carcinoma cells and suppresses tumor growth in athymic mice

CANCER, Issue 6 2005
Simeng Suy Ph.D.
Abstract BACKGROUND In previous studies, nitroxide tempo (2, 2, 6, 6-tetramethyl-piperidine-1-oxyl), a small molecule, induced cell death in cancer cells. The current study examined the antineoplastic properties of tempo in the human hormone-dependent/hormone-independent prostate carcinoma models (LNCaP, DU-145, and PC-3). METHODS The apoptotic effects of tempo were examined by the flow cytometric analysis of cells labeled with fluorescein isothiocyanate-conjugated annexin-V, and by electron microscopy. Enzymatic assays were performed to measure the activities of 2 cysteine proteases, i.e., caspase-9 and caspase-3, in tempo-treated cells. The effects of tempo on cell proliferation and on cell cycle distribution profiles were measured by the flow cytometric assay using immunofluorescent staining of incorporated 5'-bromo-2'-deoxyuridine (BrdU) coupled with 7-amino-actinomycin D (7-AAD) staining of total DNA. The number of proliferating cells was also determined independently by enzyme-linked immunosorbent assay using chemiluminescent detection of incorporated BrdU. Subcutaneous growth of human prostate carcinoma in athymic mice was monitored after intratumoral administration of tempo into tumor-bearing mice. In addition, cell viability assays were performed to compare the cytotoxic effect of a combination of doxorubicin or mitoxantrone and tempo with single agents. RESULTS Tempo treatment of prostate carcinoma cells caused a significant increase in the number of apoptotic cells compared with control groups (tempo, 2.5 mM, 24 hours: DU-145, approximately 3.4-fold; PC-3, approximately 6,7-fold; tempo 1 mM, 24 hours: LNCaP, approximately 12-fold). Tempo-induced loss of cell viability was blocked partially or completely after pretreatment of cells with actinomycin-D or cycloheximide, suggesting a de novo macromolecule synthesis-dependent mechanism of cell death. Electron microscopy revealed aggregation and marginalization of chromatin in the nuclei of a large number of tempo-treated LNCaP cells. Tempo treatment of LNCaP cells resulted in enhanced activities of caspase-9 (tempo, 5 mM, 15 hours: approximately 2-fold) and caspase-3 (tempo, 2.5 mM, 24 hours: approximately 12-fold). Tempo treatment also led to an enhanced number of cells in G2/M phase of the cell cycle (tempo, 5.0 mM, 24 hours: DU-145, approximately 1.6-fold; PC-3, approximately 1.5-fold; LNCaP, approximately 5.3-fold), and decreased BrdU incorporation indicative of a decline in the number of proliferating cells (tempo, 2.5 mM, 24 or 48 hours; DU-145, approximately 2,3-fold; PC-3, approximately 1.2-fold; LNCaP, approximately 5,10-fold). Administration of tempo into LNCaP tumor-bearing mice resulted in a significant inhibition of tumor growth (percent initial tumor volume [Day 30, n = 4]: vehicle, 845.35 ± 272.83; tempo, 9.72 ± 9.72; tempo vs. vehicle, P < 0.02). In hormone-refractory prostate carcinoma cells, a combination of relatively low doses of tempo and doxorubicin or mitoxantrone caused enhanced cytotoxicity as compared with single agents. CONCLUSIONS These data demonstrated that nitroxide tempo induced apoptosis and activated a caspase-mediated signaling pathway in prostate carcinoma cells. Tempo treatment also caused cell cycle arrest in G2/M phase and decreased the number of proliferating cells (S phase). Tempo treatment of tumor-bearing mice led to inhibition of tumor growth, suggesting that tempo is a novel member of the small-molecule family of antineoplastic agents. Cancer 2005. © 2005 American Cancer Society. [source]

Bone morphogenetic protein-10 (BMP-10) inhibits aggressiveness of breast cancer cells and correlates with poor prognosis in breast cancer

CANCER SCIENCE, Issue 10 2010
Lin Ye
Our recent study showed that a novel member of bone morphogenetic protein (BMP) family, BMP-10, was decreased in prostate cancer. In the present study, we investigated the implication of BMP-10 in breast cancer, particularly the relation of its expression with clinical aspects. The expression of BMP-10 was examined in a cohort of human breast cancer specimens (normal, n = 23; cancer, n = 97), using both quantitative real-time PCR and immunohistochemical staining. The full-length human BMP-10 was cloned into a mammalian expression plasmid vector and then transfected into breast cancer cells. The effect on growth, cell matrix adhesion, motility, and invasion of MDA-MB-231 cells by BMP-10 was then investigated using in vitro growth assays. Immunohistochemical staining and quantitative real-time PCR revealed a decreased expression of BMP-10 in breast cancer. Further analysis of BMP-10 transcript level against the clinical aspect demonstrated that the decreased BMP-10 expression correlated with disease progression, bone metastasis, and poor prognosis. The disease-free survival of the patients with a higher level of BMP-10 was 132.8 (95% CI, 122.0,143.5) months, significantly longer compared to 93.7 (95% CI, 60.3,127.2) months for patients with a lower level of BMP-10 expression (P = 0.043). The overexpression of BMP-10 has broad inhibitory effects on the in vitro growth, invasion, and motility of breast cancer cells. Taken together, BMP-10 can inhibit the cell growth of breast cancer cells, and decreased BMP-10 expression correlates to poor prognosis and disease progression, particularly the lymphatic and bone metastasis. Bone morphogenetic protein-10 (BMP-10) may function as a tumor suppressor in breast cancer. (Cancer Sci 2010) [source]

Microbial aldo-keto reductases

FEMS MICROBIOLOGY LETTERS, Issue 2 2002
Elizabeth M Ellis
Abstract The aldo-keto reductases (AKR) are a superfamily of enzymes with diverse functions in the reduction of aldehydes and ketones. AKR enzymes are found in a wide range of microorganisms, and many open reading frames encoding related putative enzymes have been identified through genome sequencing projects. Established microbial members of the superfamily include the xylose reductases, 2,5-diketo- d -gluconic acid reductases and ,-keto ester reductases. The AKR enzymes share a common (,/,)8 structure, and conserved catalytic mechanism, although there is considerable variation in the substrate-binding pocket. The physiological function of many of these enzymes is unknown, but a variety of methods including gene disruptions, heterologous expression systems and expression profiling are being employed to deduce the roles of these enzymes in cell metabolism. Several microbial AKR are already being exploited in biotransformation reactions and there is potential for other novel members of this important superfamily to be identified, studied and utilized in this way. [source]

High-Pressure Synthesis of Tantalum Nitride Having Orthorhombic U2S3 Structure

ADVANCED FUNCTIONAL MATERIALS, Issue 14 2009
Andreas Zerr
Abstract Among binary compounds, there is a high potential for discovery of novel members (polymorphic phases or compounds) of the nitrides of transition metals group due to a pronounced dependence of the oxidation state of the metals (M) on pressure. The power of high pressure,high temperature (HP-HT) route for synthesis of binary nitrides has already been demonstrated by the discovery of cubic nitrides of the group 4 and 14 elements, of crystalline polymorphs of P3N5, and by reports on formation of four noble metal nitrides. It is anticipated that such HP products exhibit, in addition to enhanced elastic and mechanical behavior, other functional properties making them interesting for industrial applications. Here, HP,HT synthesis research is extended to nitrides of group 5 elements, resulting in the discovery of a novel hard tantalum nitride, exhibiting U2S3 structure: , -Ta2N3 (Pbnm, a,=,8.1911(17),Å, b,=,8.1830(17),Å, c,=,2.9823(3),Å). The stoichiometry is supported by two independent means, verifying that , -Ta2N3 is the first thermodynamically stable transition metal nitride with a N:M ratio exceeding 4:3. Due to its high hardness and peculiar texture (needle-like and granular crystallites), , -Ta2N3 may find practical applications as a hard fracture resistant material. [source]

The impact of human herpesvirus-6 and -7 infection on the outcome of liver transplantation

LIVER TRANSPLANTATION, Issue 8 2002
Raymund R. Razonable
Human herpesvirus (HHV)-6 and -7 are novel members of the ,-herpesvirus family that maintain latency in the human host after primary infection. Reactivation from latency and/or increased degree of viral replication occurs during periods of immune dysfunction. The clinical effect of HHV-6 and HHV-7 reactivation in recipients of liver transplants is now being recognized. Clinical illnesses such as fever, rash, pneumonitis, encephalitis, hepatitis, and myelosuppression have been described in a number of anecdotal reports. Moreover, a growing body of evidence suggests that the more important effect of HHV-6 and HHV-7 reactivation on the outcomes of liver transplantation may be mediated indirectly by their interactions with the other ,-herpesvirus,cytomegalovirus (CMV). Coinfection among these three ,-herpesviruses in clinical syndromes that were classically ascribed to be solely caused by CMV has been shown and has raised substantial interest in the potential role of HHV-6 and HHV-7 as copathogens in the direct and indirect illnesses caused by CMV. This article reviews the current scientific data on the role and the magnitude of impact of HHV-6 and HHV-7 infection on the outcomes of liver transplantation. [source]

Basic characterization of 90 kDa heat shock protein genes HSP90AA1, HSP90AB1, HSP90B1 and TRAP1 expressed in Japanese quail (Coturnix japonica)

ANIMAL SCIENCE JOURNAL, Issue 4 2010
Kohji NAGAHORI
ABSTRACT In the current study, we describe four novel members of the 90 kDa heat shock protein (HSP90) family expressed in Japanese quail, Coturnix japonica. The coding regions of the genes, CjHSP90AA1, CjHSP90AB1, CjHSP90B1 and CjTRAP1, exhibited more than 94% similarity to their related genes in chicken. The putative proteins encoded by these quail genes contained motifs considered essential for HSP90 gene function. In addition, the predicted proteins were more similar to HSP90AA1, HSP90AB1, HSP90B1 and TRAP1 proteins expressed in vertebrates than they were to other members of the HSP90 family. Exon numbers of CjHSP90AA1 (11), CjHSP90AB1 (12) or CjTRAP1 (18) are the same as the chicken and mammalian orthologs. Furthermore, gene order in the regions surrounding CjHSP90AB1 and CjTRAP1 has been preserved, providing evidence that the genomic regions were orthologous to HSP90-containing regions in the chicken genome. The promoter regions of the genes also contained conserved motifs identified in related genes of chicken. However, the nucleotide sequences of the 5,-flanking region of these genes were highly polymorphic. We also found that CjHSP90AA1 exhibited a robust response to heat shock treatment. Taken together, the data suggest that CjHSP90AA1, CjHSP90AB1, CjHSP90B1 and CjTRAP1 encode orthologs of HSP90AA1, HSP90AB1, HSP90B1 and TRAP1, respectively. [source]