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Articles 1321 - 1341 of 1341
Full-Text Articles in Medical Genetics
Signaling And Regulation Of G Protein-Coupled Receptors In Airway Smooth Muscle., Charlotte K Billington, Raymond B Penn
Signaling And Regulation Of G Protein-Coupled Receptors In Airway Smooth Muscle., Charlotte K Billington, Raymond B Penn
Department of Medicine Faculty Papers
Signaling through G protein-coupled receptors (GPCRs) mediates numerous airway smooth muscle (ASM) functions including contraction, growth, and "synthetic" functions that orchestrate airway inflammation and promote remodeling of airway architecture. In this review we provide a comprehensive overview of the GPCRs that have been identified in ASM cells, and discuss the extent to which signaling via these GPCRs has been characterized and linked to distinct ASM functions. In addition, we examine the role of GPCR signaling and its regulation in asthma and asthma treatment, and suggest an integrative model whereby an imbalance of GPCR-derived signals in ASM cells contributes to the …
A Genetic Lesion That Arrests Plasma Cell Homing To The Bone Marrow, Loren D. Erickson, Ling-Li Lin, Biyan Duan, Laurence Morel, Randolph J. Noelle
A Genetic Lesion That Arrests Plasma Cell Homing To The Bone Marrow, Loren D. Erickson, Ling-Li Lin, Biyan Duan, Laurence Morel, Randolph J. Noelle
Dartmouth Scholarship
The coordinated regulation of chemokine responsiveness plays a critical role in the development of humoral immunity. After antigen challenge and B cell activation, the emerging plasma cells (PCs) undergo CXCL12-induced chemotaxis to the bone marrow, where they produce Ab and persist. Here we show that PCs, but not B cells or T cells from lupus-prone NZM mice, are deficient in CXCL12-induced migration. PC unresponsiveness to CXCL12 results in a marked accumulation of PCs in the spleen of mice, and a concordant decrease in bone marrow PCs. Unlike normal mice, in NZM mice, a majority of the splenic PCs are long-lived. …
Characterization Of Subcellular Localization And Stability Of A Splice Variant Of G Alpha I2., Philip B Wedegaertner
Characterization Of Subcellular Localization And Stability Of A Splice Variant Of G Alpha I2., Philip B Wedegaertner
Department of Microbiology and Immunology Faculty Papers
BACKGROUND: Alternative mRNA splicing of alpha(i2), a heterotrimeric G protein alpha subunit, has been shown to produce an additional protein, termed salpha(i2). In the salpha(i2) splice variant, 35 novel amino acids replace the normal C-terminal 24 amino acids of alpha(i2). Whereas alpha(i2) is found predominantly at cellular plasma membranes, salpha(i2) has been localized to intracellular Golgi membranes, and the unique 35 amino acids of salpha(i2) have been suggested to constitute a specific targeting signal. RESULTS: This paper proposes and examines an alternative hypothesis: disruption of the normal C-terminus of alpha(i2) produces an unstable protein that fails to localize to plasma …
Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky
Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky
Dartmouth Scholarship
All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor α (RARα). Microarray analyses previously revealed induction of UBE1L (ubiquitin-activating enzyme E1-like) after RA treatment of NB4 APL cells. We report here that this occurs within 3 h in RA-sensitive but not RA-resistant APL cells, implicating UBE1L as a direct retinoid target. A 1.3-kb fragment of the UBE1L promoter was capable of mediating transcriptional response to RA in a retinoid receptor-selective manner. PML/RARα, a repressor of RA target genes, abolished this UBE1L promoter activity. A hallmark of …
Transcriptional Interference By Independently Regulated Genes Occurs In Any Relative Arrangement Of The Genes And Is Influenced By Chromosomal Integration Position, Susan K. Eszterhas, Eric E. Bouhassira, David I. K. Martin, Steven Fiering
Transcriptional Interference By Independently Regulated Genes Occurs In Any Relative Arrangement Of The Genes And Is Influenced By Chromosomal Integration Position, Susan K. Eszterhas, Eric E. Bouhassira, David I. K. Martin, Steven Fiering
Dartmouth Scholarship
Transcriptional interference is the influence, generally suppressive, of one active transcriptional unit on another unit linked in cis. Its wide occurrence in experimental systems suggests that it may also influence transcription in many loci, but little is known about its precise nature or underlying mechanisms. Here we report a study of the interaction of two nearly identical transcription units juxtaposed in various arrangements. Each reporter gene in the constructs has its own promoter and enhancer and a strong polyadenylation signal. We used recombinase-mediated cassette exchange (RMCE) to insert the constructs into previously tagged genomic sites in cultured cells. This …
Evaluation Of A Tetracycline-Inducible Promoter In Staphylococcus Aureus In Vitro And In Vivo And Its Application In Demonstrating The Role Of Sigb In Microcolony Formation, B. T. Bateman, N. P. Donegan, T. M. Jarry, M. Palma
Evaluation Of A Tetracycline-Inducible Promoter In Staphylococcus Aureus In Vitro And In Vivo And Its Application In Demonstrating The Role Of Sigb In Microcolony Formation, B. T. Bateman, N. P. Donegan, T. M. Jarry, M. Palma
Dartmouth Scholarship
An inducible promoter system provides a powerful tool for studying the genetic basis for virulence. A variety of inducible systems have been used in other organisms, including pXyl-xylR-inducible promoter, the pSpac-lacI system, and the arabinose-inducible PBAD promoter, but each of these systems has limitations in its application to Staphylococcus aureus. In this study, we demonstrated the efficacy of a tetracycline-inducible promoter system in inducing gene expression in S. aureus in vitro and inside epithelial cells as well as in an animal model of infection. Using the xyl/tetO promoter::gfpuvr fusion carried on a shuttle …
Sart, A Repressor Of Α-Hemolysin In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Steven Gill, Ambrose L. Cheung
Sart, A Repressor Of Α-Hemolysin In Staphylococcus Aureus, Katherine A. Schmidt, Adhar C. Manna, Steven Gill, Ambrose L. Cheung
Dartmouth Scholarship
In searching the Staphylococcus aureus genome, we found several homologs to SarA. One of these genes, sarT, codes for a basic protein with 118 residues and a predicted molecular size of 16,096 Da. Northern blot analysis revealed that the expression of sarT was repressed by sarA and agr. An insertion sarT mutant generated in S. aureus RN6390 and 8325-4 backgrounds revealed minimal effect on the expression of sarR and sarA. The RNAIII level was notably increased in the sarT mutant, particularly in postexponential-phase cells, while the augmentative effect on RNAII was less. SarT repressed the expression of alpha-hemolysin, as determined …
A Cultivated Taste For Yeast., C Brenner
A Cultivated Taste For Yeast., C Brenner
Kimmel Cancer Center Faculty Papers
The availability of complete genomic sequences of Saccharomyces cerevisiae has catalyzed a cultural change in the practice of yeast biology, providing opportunities to develop high throughput techniques to define protein function, to define drug targets, and to discover and characterize drugs.
Interaction Between Fgf And Bmp Signaling Pathways Regulates Development Of Metanephric Mesenchyme., Andrew T. Dudley, R. E. Godin, E. J. Robertson
Interaction Between Fgf And Bmp Signaling Pathways Regulates Development Of Metanephric Mesenchyme., Andrew T. Dudley, R. E. Godin, E. J. Robertson
Journal Articles: Genetics, Cell Biology & Anatomy
Nephrogenesis in the mouse kidney begins at embryonic day 11 and ends approximately 10 days postpartum. During this period, new nephrons are continually being generated from a stem-cell population-the nephrogenic mesenchyme-in response to signals emanating from the tips of the branching ureter. Relatively little is known about the mechanism by which the nephrogenic mesenchyme cell population is maintained at the tips of the ureter in the presence of signals promoting tubulogenesis. Previous studies have shown that a loss of Bmp7 function leads to kidney defects that are a likely result of progressive loss of nephrogenic mesenchyme by apoptosis. The studies …
Phosphorylation Of Elongation Factor 1 And Ribosomal Protein S6 By Multipotential S6 Kinase And Insulin Stimulation Of Translational Elongation, Y W Chang, J A Traugh
Phosphorylation Of Elongation Factor 1 And Ribosomal Protein S6 By Multipotential S6 Kinase And Insulin Stimulation Of Translational Elongation, Y W Chang, J A Traugh
Faculty, Staff and Student Publications
Stimulation of protein synthesis in response to insulin is concomitant with increased phosphorylation of initiation factors 4B and 4G and ribosomal protein S6 (Morley, S. J., and Traugh, J. A. (1993) Biochimie 75, 985-989) and is due at least in part to multipotential S6 kinase. When elongation factor 1 (EF-1) from rabbit reticulocytes was examined as substrate for multipotential S6 kinase, up to 1 mol/mol of phosphate was incorporated into the alpha, beta, and delta subunits. Phosphorylation of EF-1 resulted in a 2-2. 6-fold stimulation of EF-1 activity, as measured by poly(U)-directed polyphenylalanine synthesis. The rate of elongation was also …
Disruption Of The Cbfa2 Gene Causes Necrosis And Hemorrhaging In The Central Nervous System And Blocks Definitive Hematopoiesis., Qing Wang, Terryl Stacy, Michael M Binder, Miguel Marin-Padilla, Arlene H. Sharpe, Nancy A. Speck
Disruption Of The Cbfa2 Gene Causes Necrosis And Hemorrhaging In The Central Nervous System And Blocks Definitive Hematopoiesis., Qing Wang, Terryl Stacy, Michael M Binder, Miguel Marin-Padilla, Arlene H. Sharpe, Nancy A. Speck
Dartmouth Scholarship
The CBFA2 (AML1) gene encodes a DNA-binding subunit of the heterodimeric core-binding factor. The CBFA2 gene is disrupted by the (8;21), (3;21), and (12;21) chromosomal translocations associated with leukemias and myelodysplasias in humans. Mice lacking a CBF alpha 2 protein capable of binding DNA die between embryonic days 11.5 and 12.5 due to hemorrhaging in the central nervous system (CNS), at the nerve/CNS interfaces of cranial and spinal nerves, and in somitic/intersomitic regions along the presumptive spinal cord. Hemorrhaging is preceded by symmetric, bilateral necrosis in these regions. Definitive erythropoiesis and myelopoiesis do not occur in Cbfa2-deficient embryos, and disruption …
A Requirement For Bone Morphogenetic Protein-7 During Development Of The Mammalian Kidney And Eye., Andrew T. Dudley, K. M. Lyons, E. J. Robertson
A Requirement For Bone Morphogenetic Protein-7 During Development Of The Mammalian Kidney And Eye., Andrew T. Dudley, K. M. Lyons, E. J. Robertson
Journal Articles: Genetics, Cell Biology & Anatomy
BMP-7/OP-1, a member of the transforming growth factor-beta (TGF-beta) family of secreted growth factors, is expressed during mouse embryogenesis in a pattern suggesting potential roles in a variety of inductive tissue interactions. The present study demonstrates that mice lacking BMP-7 display severe defects confined to the developing kidney and eye. Surprisingly, the early inductive tissue interactions responsible for establishing both organs appear largely unaffected. However, the absence of BMP-7 disrupts the subsequent cellular interactions required for their continued growth and development. Consequently, homozygous mutant animals exhibit renal dysplasia and anophthalmia at birth. Overall, these findings identify BMP-7 as an essential …
The Growth Of Simian Virus 40 (Sv40) Host Range/Adenovirus Helper Function Mutants In An African Green Monkey Cell Line That Constitutively Expresses The Sv40 Agnoprotein., Terryl P. Stacy, Michele Chamberlain, Susan Carswell, Charles N. Cole
The Growth Of Simian Virus 40 (Sv40) Host Range/Adenovirus Helper Function Mutants In An African Green Monkey Cell Line That Constitutively Expresses The Sv40 Agnoprotein., Terryl P. Stacy, Michele Chamberlain, Susan Carswell, Charles N. Cole
Dartmouth Scholarship
The simian virus 40 T-antigen carboxy-terminal mutants, dlA2459 and dlA2475, are cell line and temperature dependent for growth and plaque formation in monkey kidney cells. Although these mutants did form plaques on BSC-1 cells at 37 degrees C, they were about fivefold less efficient for plaque formation than wild-type simian virus 40. These mutants did not grow in CV-1 cells and did not synthesize agnoprotein in those cells. CV-1 cells which constitutively express the agnoprotein were permissive for mutant plaque formation. However, late mRNAs, virion proteins, and progeny virion yields did not accumulate to wild-type levels during mutant infection of …
Parentage Analysis With Genetic Markers In Natural Populations I The Expected Proportion Of Offspring With Unambiguous Paternity, R Chakraborty, T R Meagher, P E Smouse
Parentage Analysis With Genetic Markers In Natural Populations I The Expected Proportion Of Offspring With Unambiguous Paternity, R Chakraborty, T R Meagher, P E Smouse
Faculty, Staff and Student Publications
Recent studies indicate that polymorphic genetic markers are potentially helpful in resolving genealogical relationships among individuals in a natural population. Genetic data provide opportunities for paternity exclusion when genotypic incompatibilities are observed among individuals, and the present investigation examines the resolving power of genetic markers in unambiguous positive determination of paternity. Under the assumption that the mother for each offspring in a population is unambiguously known, an analytical expression for the fraction of males excluded from paternity is derived for the case where males and females may be derived from two different gene pools. This theoretical formulation can also be …
Molecular Cloning And Sequence Analysis Of The Plasmodium Falciparum Dihydrofolate Reductase-Thymidylate Synthase Gene., David J. Bzik, Wu-Bo Li, Toshihiro Horii, Joseph Inselburg
Molecular Cloning And Sequence Analysis Of The Plasmodium Falciparum Dihydrofolate Reductase-Thymidylate Synthase Gene., David J. Bzik, Wu-Bo Li, Toshihiro Horii, Joseph Inselburg
Dartmouth Scholarship
Genomic DNA clones that coded for the bifunctional dihydrofolate reductase (DHFR) and thymidylate synthase (TS) (DHFR-TS) activities from a pyrimethamine-sensitive strain of Plasmodium falciparum were isolated and sequenced. The deduced DHFR-TS protein contained 608 amino acids (71,682 Da). The coding region for DHFR-TS contained no intervening sequences and had a high A + T content (75%). The DHFR domain, in the amino-terminal portion of the protein, was joined by a 94-amino acid junction sequence to the TS domain in the carboxyl-terminal portion of the protein. The TS domain was more conserved than the DHFR domain and both P. falciparum domains …
Fine-Structure Analysis Of The Processing And Polyadenylation Region Of The Herpes Simplex Virus Type 1 Thymidine Kinase Gene By Using Linker Scanning, Internal Deletion, And Insertion Mutations., Fang Zhang, Roger M. Denome, Charles N. Cole
Fine-Structure Analysis Of The Processing And Polyadenylation Region Of The Herpes Simplex Virus Type 1 Thymidine Kinase Gene By Using Linker Scanning, Internal Deletion, And Insertion Mutations., Fang Zhang, Roger M. Denome, Charles N. Cole
Dartmouth Scholarship
Most eucaryotic mRNAs are polyadenylated. In higher eucaryotes, the sequence AATAAA is located 7 to 30 base pairs (bp) upstream from the site of processing and polyadenylation and is a critical part of the signal for processing and polyadenylation. Efficient cleavage and polyadenylation also require sequences downstream of polyadenylation sites. The herpes simplex virus type 1 thymidine kinase (tk) gene contains two copies of the AATAAA hexanucleotide and a GT box (18 of 19 consecutive residues are G or T) previously shown to be required for efficient processing and polyadenylation of tk mRNA (C. N. Cole and T. P. Stacy, …
Identification Of Sequences In The Herpes Simplex Virus Thymidine Kinase Gene Required For Efficient Processing And Polyadenylation., Charles N. Cole, Terryl P. Stacy
Identification Of Sequences In The Herpes Simplex Virus Thymidine Kinase Gene Required For Efficient Processing And Polyadenylation., Charles N. Cole, Terryl P. Stacy
Dartmouth Scholarship
The herpes simplex virus (HSV) type 1 thymidine kinase gene (tk) was resected from its 3' end with BAL 31 exonuclease. Two sets of plasmids were isolated that lacked information distal to the two copies of the hexanucleotide 5'-AATAAA-3' located at the 3' end of the HSV tk gene. The presence of a simian virus 40 origin of DNA replication in each plasmid facilitated analysis of patterns of transcription in transfected Cos-1 monkey cells. Transcription analyses were performed with an S1 nuclease protection assay. Efficient processing and polyadenylation at the normal site still occurred when all sequences more than 44 …
Two Separable Functional Domains Of Simian Virus 40 Large T Antigen: Carboxyl-Terminal Region Of Simian Virus 40 Large T Antigen Is Required For Efficient Capsid Protein Synthesis., Joanne Tornow, Maryellen Polvino-Bodnar, George Santangelo, Charles N. Cole
Two Separable Functional Domains Of Simian Virus 40 Large T Antigen: Carboxyl-Terminal Region Of Simian Virus 40 Large T Antigen Is Required For Efficient Capsid Protein Synthesis., Joanne Tornow, Maryellen Polvino-Bodnar, George Santangelo, Charles N. Cole
Dartmouth Scholarship
The carboxyl-terminal portion of simian virus 40 large T antigen is essential for productive infection of CV-1 and CV-1p green monkey kidney cells. Mutant dlA2459, lacking 14 base pairs at 0.193 map units, was positive for viral DNA replication, but unable to form plaques in CV-1p cells (J. Tornow and C.N. Cole, J. Virol. 47:487-494, 1983). In this report, the defect of dlA2459 is further defined. Simian virus 40 late mRNAs were transcribed, polyadenylated, spliced, and transported in dlA2459-infected cells, but the level of capsid proteins produced in infected CV-1 green monkey kidney cells was extremely low. dlA2459 large T …
Genetically Controlled Variation Of “Acid” Beta-Galactosidase Detected In Rattus Norvegicus By Isoelectric Focusing, T C Douglas, K A Kimmel, P E Dawson
Genetically Controlled Variation Of “Acid” Beta-Galactosidase Detected In Rattus Norvegicus By Isoelectric Focusing, T C Douglas, K A Kimmel, P E Dawson
Faculty, Staff and Student Publications
Two genetically variant forms of rat "acid" beta-galactosidase were found to differ in isoelectric point and pH dependence, but not in thermostability or sensitivity to inhibition by p-mercuribenzoate (PMB). The results of two backcrosses and an intercross indicated that the isoelectric focusing phenotypes are controlled by two codominant alleles at a single autosomal locus, for which we propose the name Glb-1. No significant linkage between Glb-1 and albino (LG I), brown (LG II), or hooded (LG VI) was observed. Strain-specific differences in total levels of kidney beta-galactosidase were detected, but it is not yet known whether the variation is controlled …
Polymorphisms, Linkage And Mapping Of Four Enzyme Loci In The Fish Genus Xiphophorus (Poeciliidae), D C Morizot, M J Siciliano
Polymorphisms, Linkage And Mapping Of Four Enzyme Loci In The Fish Genus Xiphophorus (Poeciliidae), D C Morizot, M J Siciliano
Faculty, Staff and Student Publications
Electrophoretic variants at four additional enzyme loci--two esterases (Est-2, Est-3), retinal lactate dehydrogenase (LDH-1) and mannose phosphate isomerase (MPI)--among three species and four subspecies of fish of the genus Xiphophorus were observed. Electrophoretic patterns in F1 hybrid heterozygotes confirmed the monomeric structures of MPI and the esterase and the tetrametric structure of LDH in these fishes. Variant alleles of all four loci displayed normal Mendelian segregation in backcross and F2 hybrids. Recombination data from backcross hybrids mapped with Haldane's mapping function indicate the four loci to be linked as Est-2--0.43--Est3--0.26--LDH-1--0.19--MPI. Significant interference was detected and apparently concentrated in the Est-3 …
Three Linked Enzyme Loci In Fishes: Implications In The Evolution Of Vertebrate Chromosomes, D C Morizot, D A Wright, M J Siciliano
Three Linked Enzyme Loci In Fishes: Implications In The Evolution Of Vertebrate Chromosomes, D C Morizot, D A Wright, M J Siciliano
Faculty, Staff and Student Publications
A three-point linkage group comprised of loci coding for adenosine deaminase (ADA), glucose-6-phosphate dehydrogenase (G6PDH), and 6-phospho-gluconate dehydrogenase (6PGD) is described in fish of the genus Xiphophorus (Poeciliidae). The alleles at loci in this group were shown to assort independently from the alleles at three other loci--isocitrate dehydrogenase 1 and 2, and glyceraldehyde-3-phosphate dehydrogenase 1. Alleles at the latter three loci also assort independently from each other. Data were obtained by observing the segregation of electrophoretically variant alleles in reciprocal backcross hybrids derived from crosses between either X. helleri guentheri or X. h. strigatus and X. maculatus. The linkage component …