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Articles 61 - 75 of 75

Full-Text Articles in Medical Biochemistry

Circadian Clock-Specific Roles For The Light Response Protein White Collar-2, Michael A. Collett, Jay C. Dunlap, Jennifer J. Loros Apr 2001

Circadian Clock-Specific Roles For The Light Response Protein White Collar-2, Michael A. Collett, Jay C. Dunlap, Jennifer J. Loros

Dartmouth Scholarship

To understand the role of white collar-2 in theNeurospora circadian clock, we examined alleles ofwc-2 thought to encode partially functional proteins. We found that wc-2 allele ER24 contained a conservative mutation in the zinc finger. This mutation results in reduced levels of circadian rhythm-critical clock gene products, frq mRNA and FRQ protein, and in a lengthened period of the circadian clock. In addition, this mutation altered a second canonical property of the clock, temperature compensation: as temperature increased, period length decreased substantially. This temperature compensation defect correlated with a temperature-dependent increase in overall FRQ protein levels, with the …


Title, Fergus Ryan, D Devaney, Caroline Joyce, A Nestorowicz, M Permutt, Benjamin Glaser, Paul Thornton, David E. Barton Jan 1998

Title, Fergus Ryan, D Devaney, Caroline Joyce, A Nestorowicz, M Permutt, Benjamin Glaser, Paul Thornton, David E. Barton

Articles

Persistent hypoglycaemia in infancy is most commonly caused by hyperinsulinism. A case is reported of the somatic loss of the maternal 11p in an insulin secreting focal adenoma in association with a germline SUR-1mutation on the paternal allele in a baby boy with hyperinsulinism diagnosed at 49 days old. A reduction to homozygosity of an SUR-1 mutation is proposed as a critical part of the cause of focal hyperinsulinism.


Dissection Of A Circadian Oscillation Into Discrete Domains, Martha W. Merrow, Norman Y. Garceau, Jay C. Dunlap Apr 1997

Dissection Of A Circadian Oscillation Into Discrete Domains, Martha W. Merrow, Norman Y. Garceau, Jay C. Dunlap

Dartmouth Scholarship

The circadian oscillator in Neurospora is a negative feedback loop involving as principal players the products of the frequency (frq) locus. frq encodes multiple forms of its protein product FRQ, which act to depress the amounts of frq transcript. In this scheme there are two discrete and separable steps to the circadian cycle, negative feedback itself (repression) in which FRQ acts to decrease the levels of its own transcript, and recovery from repression (derepression) in which frq transcript levels return to peak amounts. By introducing an exogenously regulatable frq transgene into a frq loss-of-function strain (frq9 …


Transcriptional Activity Of Core Binding Factor-Alpha (Aml1) And Beta Subunits On Murine Leukemia Virus Enhancer Cores., Ari L. Zaiman, Amy F. Lewis, Barbara E. Crute, N. A. Speck, Jack Lenz May 1995

Transcriptional Activity Of Core Binding Factor-Alpha (Aml1) And Beta Subunits On Murine Leukemia Virus Enhancer Cores., Ari L. Zaiman, Amy F. Lewis, Barbara E. Crute, N. A. Speck, Jack Lenz

Dartmouth Scholarship

Core binding factor (CBF), also known as polyomavirus enhancer-binding protein 2 and SL3 enhancer factor 1, is a mammalian transcription factor that binds to an element termed the core within the enhancers of the murine leukemia virus family of retroviruses. The core elements of the SL3 virus are important genetic determinants of the ability of this virus to induce T-cell lymphomas and the transcriptional activity of the viral long terminal repeat in T lymphocytes. CBF consists of two subunits, a DNA binding subunit, CBF alpha, and a second subunit, CBF beta, that stimulates the DNA binding activity of CBF alpha. …


The Leukemic Core Binding Factor Beta-Smooth Muscle Myosin Heavy Chain (Cbf Beta-Smmhc) Chimeric Protein Requires Both Cbf Beta And Myosin Heavy Chain Domains For Transformation Of Nih 3t3 Cells., Amitav Hajra, Pu Liu, Qing Wang, Christine Kelley Mar 1995

The Leukemic Core Binding Factor Beta-Smooth Muscle Myosin Heavy Chain (Cbf Beta-Smmhc) Chimeric Protein Requires Both Cbf Beta And Myosin Heavy Chain Domains For Transformation Of Nih 3t3 Cells., Amitav Hajra, Pu Liu, Qing Wang, Christine Kelley

Dartmouth Scholarship

An inversion of chromosome 16 associated with the M4Eo subtype of acute myeloid leukemia produces a chimeric protein fusing the beta subunit of the transcription factor core binding factor (CBF beta) to the tail region of smooth muscle myosin heavy chain (SMMHC). We investigated the oncogenic properties of this CBF beta-SMMHC chimeric protein using a 3T3 transformation assay. NIH 3T3 cells expressing CBF beta-SMMHC acquired a transformed phenotype, as indicated by their ability to form foci, grow in soft agarose, and form tumors in nude mice. Cells expressing normal CBF beta or the SMMHC tail domain did not become transformed. …


A Phorbol Ester Response Element Within The Human T-Cell Receptor Beta-Chain Enhancer., Haydn M. Prosser, David Wotton, Anne Gegonne, Jacques Ghysdael, Shuwen Wang, Nancy A. Speck, Michael J. Owen Oct 1992

A Phorbol Ester Response Element Within The Human T-Cell Receptor Beta-Chain Enhancer., Haydn M. Prosser, David Wotton, Anne Gegonne, Jacques Ghysdael, Shuwen Wang, Nancy A. Speck, Michael J. Owen

Dartmouth Scholarship

The activity of the T-cell receptor beta-chain gene enhancer is increased by activators of the protein kinase C pathway during T-cell activation. Analysis of mutant enhancer constructs identified two elements, beta E2 and beta E3, conferring phorbol ester inducibility. Multimerized beta E2 acted in isolation as a phorbol ester-responsive element. Both beta E2 and beta E3, which contain a consensus Ets-binding site, were shown to bind directly to the product of the c-ets-1 protooncogene. Both regions also bound a second factor, core-binding factor. Mutation of the beta E2 Ets site abolished the inducibility of the beta E2 multimer. beta E2 …


Characterization Of The Formate (For) Locus, Which Encodes The Cytosolic Serine Hydroxymethyltransferase Of Neurospora Crassa., C. Robertson Mcclung, Cynthia R. Davis, Karen M. Page, Sylvia A. Denome Apr 1992

Characterization Of The Formate (For) Locus, Which Encodes The Cytosolic Serine Hydroxymethyltransferase Of Neurospora Crassa., C. Robertson Mcclung, Cynthia R. Davis, Karen M. Page, Sylvia A. Denome

Dartmouth Scholarship

Serine hydroxymethyltransferase (SHMT) occupies a central position in one-carbon (C1) metabolism, catalyzing the reaction of serine and tetrahydrofolate to yield glycine and 5,10-methylenetetrahydrofolate. Methylenetetrahydrofolate serves as a donor of C1 units for the synthesis of numerous compounds, including purines, thymidylate, lipids, and methionine. We provide evidence that the formate (for) locus of Neurospora crassa encodes cytosolic SHMT. The for+ gene was localized to a 2.8-kb BglII fragment by complementation (restoration to formate-independent growth) of a strain carrying a recessive for allele, which confers a growth requirement for formate. The for+ gene encodes a polypeptide of 479 amino acids which shows …


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 Jul 1990

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 …


Simian Virus 40 Host Range/Helper Function Mutations Cause Multiple Defects In Viral Late Gene Expression., Terryl Stacy, Michele Chamberlain, Charles N. Cole Dec 1989

Simian Virus 40 Host Range/Helper Function Mutations Cause Multiple Defects In Viral Late Gene Expression., Terryl Stacy, Michele Chamberlain, Charles N. Cole

Dartmouth Scholarship

Simian virus 40 (SV40) deletion mutants dlA2459 and dlA2475 express T antigens that lack the normal carboxy terminus. These mutants are called host range/helper function (hr/hf) mutants because they form plaques at 37 degrees C on BSC-1 and Vero monkey kidney cell lines but not on CV-1p monkey kidney cells. Wild-type SV40 can provide a helper function to permit growth of human adenoviruses in monkey kidney cells; the hr/hf mutants cannot. Progeny yields of hr/hf mutants are also cold sensitive in all cell lines tested. Patterns of viral macromolecular synthesis in three cell lines (Vero, BSC-1, and CV-1) at three …


Linker Insertion Mutants Of Simian Virus 40 Large T Antigen That Show Trans-Dominant Interference With Wild-Type Large T Antigen Map To Multiple Sites Within The T-Antigen Gene., Jiyue Y. Zhu, Charles N. Cole Nov 1989

Linker Insertion Mutants Of Simian Virus 40 Large T Antigen That Show Trans-Dominant Interference With Wild-Type Large T Antigen Map To Multiple Sites Within The T-Antigen Gene., Jiyue Y. Zhu, Charles N. Cole

Dartmouth Scholarship

Linker insertion mutants affecting the simian virus 40 (SV40) large tumor (T) antigen were constructed by inserting a 12-base-pair oligonucleotide linker into restriction endonuclease cleavage sites located within the early region of SV40. One mutant, with the insertion at amino acid 5, was viable in CV-1p and BSC-1 cells, indicating that sequences very close to the amino terminus of large T could be altered without affecting the lytic infection cycle of SV40. All other mutants affecting large T were not viable. In complementation assays between the linker insertion mutants and either a late-gene mutant, dlBC865, or a host range/helper function …


Patterns Of Polyadenylation Site Selection In Gene Constructs Containing Multiple Polyadenylation Signals., Roger Denome, Charles Cole Nov 1988

Patterns Of Polyadenylation Site Selection In Gene Constructs Containing Multiple Polyadenylation Signals., Roger Denome, Charles Cole

Dartmouth Scholarship

We have constructed a series of plasmids containing multiple polyadenylation signals downstream of the herpes simplex virus type 1 (HSV) thymidine kinase (tk)-coding region. The signals used were from the simian virus 40 (SV40) late gene, the HSV tk gene, and an AATAAA-containing segment of the SV40 early region. This last fragment signals polyadenylation poorly in our constructs and not at all during SV40 infection. All plasmids contained the SV40 origin of replication. Plasmids were transfected into Cos-1 cells; after 48 h, cytoplasmic RNA was isolated and the quantity and 3'-end structure of tk mRNAs was analyzed by using S1 …


Molecular Cloning And Sequence Analysis Of The Plasmodium Falciparum Dihydrofolate Reductase-Thymidylate Synthase Gene., David J. Bzik, Wu-Bo Li, Toshihiro Horii, Joseph Inselburg Dec 1987

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 Dec 1986

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 Aug 1985

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 Feb 1985

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 …