Genetic Interactions between the Coagulation and Fibrinolytic Systems

2001 ◽  
Vol 86 (07) ◽  
pp. 130-137 ◽  
Author(s):  
Jay Degen
Keyword(s):  
Associated Factors ◽  
Genetic Interactions ◽  
Phenotypic Characterization ◽  
System Components ◽  
Genes Encoding ◽  
Hemostatic Factors ◽  
Mouse Lines ◽  
Made In

SummaryNearly all of the genes encoding the established coagulation and fibrinolytic factors have been successfully altered or disrupted in transgenic mice. Although comprehensive studies of each of these genetargeted mouse lines are still ongoing, the initial findings have significantly refined our understanding of the roles of selected hemostatic factors in vivo, and occasionally altered long-standing concepts. This review summarizes some of the progress that has been made in the generation and phenotypic characterization of mice lacking key hemostatic factors, including coagulation, fibrinolytic, platelet and endothelial cell-associated factors. New insights regarding the role(s) and interplay of hemostatic factors that have emerged from detailed studies of mice carrying multiple deficits in coagulation and fibrinolytic system components are highlighted.

Drosophila brachyenteron regulates gene activity and morphogenesis in the gut

Development ◽  
1996 ◽  
Vol 122 (12) ◽  
pp. 3707-3718 ◽  
Author(s):  
J.B. Singer ◽  
R. Harbecke ◽  
T. Kusch ◽  
R. Reuter ◽  
J.A. Lengyel
Keyword(s):  
Genetic Locus ◽  
Malpighian Tubules ◽  
Gene Activity ◽  
Phenotypic Characterization ◽  
Gut Development ◽  
Allelic Series ◽  
Genes Encoding

Chromosomal region 68D/E is required for various aspects of Drosophila gut development; within this region maps the Brachyury homolog T-related gene (Trg), DNA of which rescues the hindgut defects of deficiency 68D/E. From a screen of 13,000 mutagenized chromosomes we identified six non-complementing alleles that are lethal over deficiencies of 68D/E and show a hindgut phenotype. These mutations constitute an allelic series and are all rescued to viability by a Trg transgene. We have named the mutant alleles and the genetic locus they define brachyenteron (byn); phenotypic characterization of the strongest alleles allows determination of the role of byn in embryogenesis. byn expression is activated by tailless, but byn does not regulate itself. byn expression in the hindgut and anal pad primordia is required for the regulation of genes encoding transcription factors (even-skipped, engrailed, caudal, AbdominalB and orthopedia) and cell signaling molecules (wingless and decapentaplegic). In byn mutant embryos, the defective program of gene activity in these primordia is followed by apoptosis (initiated by reaper expression and completed by macrophage engulfment), resulting in severely reduced hindgut and anal pads. Although byn is not expressed in the midgut or the Malpighian tubules, it is required for the formation of midgut constrictions and for the elongation of the Malpighian tubules.

scholarly journals Construction and Phenotypic Characterization of an Auxotrophic Mutant of Mycobacterium tuberculosis Defective in l-Arginine Biosynthesis

2002 ◽  
Vol 70 (6) ◽  
pp. 3080-3084 ◽  
Author(s):  
Bhavna G. Gordhan ◽  
Debbie A. Smith ◽  
Heidi Alderton ◽  
Ruth A. McAdam ◽  
Gregory J. Bancroft ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mutant Strain ◽  
Auxotrophic Mutant ◽  
Phenotypic Characterization ◽  
Wild Type ◽  
Arginine Biosynthesis ◽  
High Concentrations

ABSTRACT A mutant of Mycobacterium tuberculosis defective in the metabolism of l-arginine was constructed by allelic exchange mutagenesis. The argF mutant strain required exogenous l-arginine for growth in vitro, and in the presence of 0.96 mM l-arginine, it achieved a growth rate and cell density in stationary phase comparable to those of the wild type. The mutant strain was also able to grow in the presence of high concentrations of argininosuccinate, but its auxotrophic phenotype could not be rescued by l-citrulline, suggesting that the ΔargF::hyg mutation exerted a polar effect on the downstream argG gene but not on argH. The mutant strain displayed reduced virulence in immunodeficient SCID mice and was highly attenuated in immunocompetent DBA/2 mice, suggesting that l-arginine availability is restricted in vivo.

scholarly journals Characterization of an L-Ascorbate Catabolic Pathway with Unprecedented Enzymatic Transformations

2019 ◽  
Author(s):  
Tyler Stack ◽  
Katelyn Morrison ◽  
Thomas Dettmer ◽  
Brendan Wille ◽  
Chan Kim ◽  
...  
Keyword(s):  
Ralstonia Eutropha ◽  
Sequence Similarity ◽  
Catabolic Genes ◽  
Genes Encoding ◽  
Benzilic Acid ◽  
Amidohydrolase Superfamily ◽  
Sequence Similarity Networks

<p>L-Ascorbate (vitamin C) is ubiquitous in both our diet and the environment. <i>Ralstonia eutropha </i>H16 (<i>Cupriavidus necator </i>ATCC 17699) uses L-ascorbate as sole carbon source but lacks the genes encoding the known catabolic pathways. RNAseq identified eight candidate catabolic genes. Sequence similarity networks and genome neighborhood networks guided predictions for function of the encoded proteins; the predictions were confirmed by <i>in vitro</i> assays and <i>in vivo</i> growth phenotypes of gene deletion mutants. L-Ascorbate, a lactone, is oxidized and ring-opened by enzymes in the cytochrome b<sub>561</sub> and gluconolactonase families, respectively, to form 2,3-diketo-L-gulonate. A protein predicted to have a WD40-like fold catalyzes an unprecedented benzilic acid rearrangement involving migration of a carboxylate group to form 2-carboxy-L-lyxonolactone; the lactone is hydrolyzed by a member of the amidohydrolase superfamily to yield 2-carboxy-L-lyxonate. A member of the PdxA family of oxidative decarboxylases catalyzes a novel decarboxylation that uses NAD<sup>+</sup> catalytically. The product, L-lyxonate, is catabolized to alpha-ketoglutarate by a previously characterized pathway.</p>

scholarly journals Gene Models, Expression Repertoire, and Immune Response of Plasmodium vivax Reticulocyte Binding Proteins

2015 ◽  
Vol 84 (3) ◽  
pp. 677-685 ◽  
Author(s):  
Jenni Hietanen ◽  
Anongruk Chim-ong ◽  
Thanprakorn Chiramanewong ◽  
Jakub Gruszczyk ◽  
Wanlapa Roobsoong ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Significant Negative Correlation ◽  
Protein Coding ◽  
Content Type ◽  
Immune Pressure ◽  
The Family ◽  
Genes Encoding ◽  
Gene Models

Members of thePlasmodium vivaxreticulocyte binding protein (PvRBP) family are believed to mediate specific invasion of reticulocytes byP. vivax. In this study, we performed molecular characterization of genes encoding members of this protein family. Through cDNA sequencing, we constructed full-length gene models and verified genes that are protein coding and those that are pseudogenes. We also used quantitative PCR to measure theirin vivotranscript abundances in clinicalP. vivaxisolates. Like genes encoding related invasion ligands ofP. falciparum,Pvrbpexpression levels vary broadly across different parasite isolates. Through antibody measurements, we found that host immune pressure may be the driving force behind the distinctly high diversity of one of the family members, PvRBP2c. Mild yet significant negative correlation was found between parasitemia and the PvRBP2b antibody level, suggesting that antibodies to the protein may interfere with invasion.

In vivo bone metastases, osteoclastogenic ability, and phenotypic characterization of human breast cancer cells

Bone ◽  
2004 ◽  
Vol 34 (4) ◽  
pp. 697-709 ◽  
Author(s):  
Nadia Rucci ◽  
Enrico Ricevuto ◽  
Corrado Ficorella ◽  
Maurizio Longo ◽  
Marie Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Phenotypic Characterization ◽  
Human Breast Cancer Cells ◽  
Human Breast

scholarly journals A homolog of human transcription factor NF-X1 encoded by the Drosophila shuttle craft gene is required in the embryonic central nervous system.

1996 ◽  
Vol 16 (1) ◽  
pp. 192-201 ◽  
Author(s):  
N D Stroumbakis ◽  
Z Li ◽  
P P Tolias
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transcription Factor ◽  
Consensus Sequence ◽  
Preliminary Evidence ◽  
Phenotypic Characterization ◽  
Binding Motif ◽  
New Family

NF-X1 is a novel cytokine-inducible transcription factor that has been implicated in the control of immune responses in humans, presumably by regulating expression of class II major histocompatibility genes. Here we report the cloning and genetic characterization of the first reported NF-X1 homolog, which is encoded by the Drosophila melanogaster shuttle craft (stc) gene. The deduced sequence of the fly and human proteins defines a new family of molecules distinguished by a novel cysteine-rich DNA-binding motif (consisting of seven copies of the consensus sequence Cx3Cx3LxCGx0-5HxCx3CHxGxCx2Cx7-9CxC). We have identified and begun a phenotypic characterization of mutations in the stc gene. stc mutants die at the end of embryogenesis, when they appear to be incapable of coordinating the typical peristaltic contraction waves normally required for embryos to hatch into feeding first instar larvae. Preliminary evidence indicates that the resulting lethality of this behavioral defect is accompanied by subtle morphological abnormalities in the central nervous system, where in wild-type embryos, STC protein is normally localized in the nuclei of repeated cell clusters within each neuromere and brain lobe. Thus, the NF-X1 homolog encoded by the Drosophila stc gene defines a new family of putative transcription factors and plays an essential role in the completion of embryonic development. This study presents the first in vivo genetic analysis of a member of this new protein family.

scholarly journals Age-Dependent Changes in Susceptibility of Suckling Mice to Individual Strains of Helicobacter pylori

2005 ◽  
Vol 73 (2) ◽  
pp. 1232-1234 ◽  
Author(s):  
Hiroyuki Suto ◽  
Maojun Zhang ◽  
Douglas E. Berg
Keyword(s):  
Helicobacter Pylori ◽  
Suckling Mice ◽  
Age Dependent ◽  
H Pylori ◽  
In Vivo Characterization ◽  
Mouse Lines

ABSTRACT To model establishment of Helicobacter pylori infection in infants, suckling mice were inoculated with mixtures of strains that preferentially colonize different gastric regions and coexist in vivo. Characterization of H. pylori recovered 2 weeks later showed that susceptibility begins earlier for some strains than for others and that the onset of susceptibility varies among mouse lines.

General summary

1969 ◽  
Vol 173 (1032) ◽  
pp. 443-445 ◽  
Keyword(s):  
Blood Clotting ◽  
Chemical Characterization ◽  
Clotting System ◽  
Red Cell Membrane ◽  
Isolation And Purification ◽  
Enzymatic Action ◽  
Physico Chemical ◽  
Made In

The blood clotting, fibrinolytic, renin–angiotensin, kinin forming systems, and complements are all systems of greater or lesser complexity. Complement with its nine components, with one of the components of human complement, C'1 consisting of three subcomponents, is the most complex; the intrinsic blood clotting mechanism running it a very close second, if not a dead heat. In addition, in each system it is necessary to consider varying number of inhibitors and activators. In no system have all the components of that system been fully characterized, although excellent progress on this score has been made in regard to the blood clotting system and complement. The need for the isolation, purification and thoroughgoing physico-chemical characterization of the components of the kinin forming system is pressing. For it is only by such characterization, and by reconstitution of the system with pure, individual components that the present hypothesis as to the sequence of reactions in this system will be supported or refuted, and the nature and significance of the reported heterogeneity of kallikrein (kininogenase) PF(dil) (PF), and kininogen, be understood. Similarly, it is only through isolation and purification that the nature of the plasminogen activators of plasma and of tissue will be ultimately clarified. Although such isolation and purification will not solve the questions of the in vivo nature and significance of these systems it will aid mightily in their solution. The enzymes in each of the five systems are broadly of the same kind, being mainly proteases, or peptidases. However, with complement recent evidence to be published shortly in the Journal of Immunology indicates, that in addition to the proteolytic activity of C'3, there is also an enzymatic action of either C'8 or C'9 on the phospholipids of the red cell membrane.

The role of the yolk syncytial layer in germ layer patterning in zebrafish

Development ◽  
2000 ◽  
Vol 127 (21) ◽  
pp. 4681-4689 ◽  
Author(s):  
S. Chen ◽  
D. Kimelman
Keyword(s):  
Related Factor ◽  
Homeodomain Protein ◽  
Germ Layer ◽  
Cell Stage ◽  
Yolk Syncytial Layer ◽  
Genes Encoding ◽  
The Stability

Formation of the three germ layers requires a series of inductive events during early embryogenesis. Studies in zebrafish indicate that the source of these inductive signals may be the extra-embryonic yolk syncytial layer (YSL). The characterization of genes encoding the nodal-related factor, Squint, and homeodomain protein, Bozozok, both of which are expressed in the YSL, suggested that the YSL has a role in mesendoderm induction. However, these genes, and a second nodal-related factor, cyclops, are also expressed in the overlying marginal blastomeres, raising the possibility that the marginal blastomeres can induce mesendodermal genes independently of the YSL. We have developed a novel technique to study signaling from the YSL in which we specifically eliminate RNAs in the YSL, thus addressing the in vivo requirement of RNA-derived signals from this region in mesendoderm induction. We show that injection of RNase into the yolk cell after the 1K cell stage (3 hours) effectively eliminates YSL transcripts without affecting ubiquitously expressed genes in the blastoderm. We also present data that indicate the stability of existing proteins in the YSL is unaffected by RNase injection. Using this technique, we show that RNA in the YSL is required for the formation of ventrolateral mesendoderm and induction of the nodal-related genes in the ventrolateral marginal blastomeres, revealing the presence of an unidentified inducing signal released from the YSL. We also demonstrate that the dorsal mesoderm can be induced independently of signals from the YSL and present evidence that this is due to the stabilization of (β)-catenin in the dorsal marginal blastomeres. Our results demonstrate that germ layer formation and patterning in zebrafish uses a combination of YSL-dependent and -independent inductive events.

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