Primary structure and expression studies of the dihydrofolate reductase gene (DFRI) of Saccharomyces cerevisiae

The nucleotide sequence of a genomic DNA fragment thought previously to contain the dihydrofolate reductase gene (DFR1) of Saccharomyces cerevisiae by genetic criteria was determined. This DNA fragment of 1784' basepairs contains a large open reading frame from position 800 to 1432, which encodes a enzyme with a predicted molecular weight of 24,229.8 Daltons. Analysis of the amino acid sequence of this protein revealed that the yeast polypep·tide contained 211 amino acids, compared to the 186 residues commonly found in the polypeptides of other eukaryotes. The difference in size of the gene product can be attributed mainly to an insert in the yeast gene. Within this region, several consensus sequences required for processing of yeast nuclear and class II mitochondrial introns were identified, but appear not sufficient for the RNA splicing. The primary structure of the yeast DHFR protein has considerable sequence homology with analogous polypeptides from other organisms, especially in the consensus residues involved in cofactor and/or inhibitor binding. Analysis of the nucleotide sequence also revealed the presence of a number of canonical sequences identified in yeast as having some function in the regulation of gene expression. These include UAS elements (TGACTC) required for tIle amino acid general control response, and "TATA H boxes as well as several consensus sequences thought to be required for transcriptional termination and polyadenylation. Analysis of the codon usage of the yeast DFRl coding region revealed a codon bias index of 0.0083. this valve very close to zero suggestes 3 that the gene is expressed at a relatively low level under normal physiological conditions. The information concerning the organization of the DFRl were used to construct a variety of fusions of its 5' regulatory region with the coding region of the lacZ gene of E. coli. Some of such fused genes encoded a fusion product that expressed in E.coli and/or in yeast under the control of the 5' regulatory elements of the DFR1. Further studies with these fusion constructions revealed that the beta-galactosidase activity encoded on multicopy plasmids was stimulated transiently by prior exposure of yeast host cells to UV light. This suggests that the yeast PFRl gene is indu.ced by UV light and nlay in1ply a novel function of DHFR protein in the cellular responses to DNA damage. Another novel f~ature of yeast DHFR was revealed during preliminary studies of a diploid strain containing a heterozygous DFRl null allele. The strain was constructed by insertion of a URA3 gene within the coding region of DFR1. Sporulation of this diploid revealed that meiotic products segregated 2:0 for uracil prototrophy when spore clones were germinated on medium supplemented with 5-formyltetrahydrofolate (folinic acid). This finding suggests that, in addition to its catalytic activity, the DFRl gene product nlay play some role in the anabolisln of folinic acid. Alternatively, this result may indicate that Ura+ haploid segregants were inviable and suggest that the enzyme has an essential cellular function in this species.

The relationship between body mass index and breast cancer recurrence/progression and breast cancer-specific death

The aim of this study was to describe the nonlinear association between body mass index (BMI) and breast cancer outcomes and to determine whether BMI improves prediction of outcomes. A cohort of906 breast cancer patients diagnosed at Henry Ford Health System, Detroit (1985-1990) were studied. The median follow-up was 10 years. Multivariate logistic regression was used to model breast cancer recurrence/progression and breast cancer-specific death. Restricted cubic splines were used to model nonlinear effects. Receiver operator characteristic areas under the curves (ROC AUC) were used to evaluate prediction. BMI was nonlinearly associated with recurrence/progression and death (p= 0.0230 and 0.0101). Probability of outcomes increased with increase or decrease ofBMI away from 25. BMI splines were suggestive of improved prediction of death. The ROC AUCs for nested models with and without BMI were 0.8424 and 0.8331 (p= 0.08). I f causally associated, modifying patients BMI towards 25 may improve outcomes.

Name Index

Index of names for the Survey of Lands for the Welland Canal Company. The index includes names for people whos lands were surveyed on the line of the canal. The index also includes a very basic geographic location of the lands in reference to the canal (for example, east, west, resevoir. No page numbers are listed.

Welland Canal Survey of Lands Name Index Page 2

Index of names for the Welland Canal Company's Survey of Land book, 1826. Includes persons name, land cultivated, uncultivated, total land and remarks. The remarks noted include; who surveyed the lands, the dates of the survey, former property names, additional property features etc.The page is titled: Statement of Lands Surveyed and appropriated to the use of the Welland Canal Company.

Welland Canal Survey of Lands Name Index Page 4

This is an index of all the names contained within the Survey of Lands. The names are listed in alphabetical order and are paired with page numbers where more information can be found on the individuals listed. This page lists names beginning with "A" through to an including "N".

Welland Canal Survey of Lands Name Index Page 5

This is an index of all the names contained within the Survey of Lands. The names are listed in alphabetical order and are paired with page numbers where more information can be found on the individuals listed. This page lists names beginning with "O" through to an including "Z".

The Weekly Register - March 1813 and Index

Issues for the March 1813 Weekly Register newspaper (Baltimore, Maryland) are divided and includes the following War of 1812 related stories: March 6th, pages 1-16: Editor's proclamation on reporting on the war (p.1); Declaration of British Parliament - 9 January 1813 (pp.1-6); President's message to Senate and House of Representatives - February 24 (p.8); Events of the War including reports from Ogdensburgh,Battle of Frenchtown with Brigadier General James Winchester, Colonel Henry Proctor, and Round Head; (pp.9-13); naval events (pp.13-15); President Madison's speech - March 4 (pp.15-16). March 13th, pages 17-40 March 20th, pages 41-56 March 27th, pages 57-72 PLEASE CLICK ON THE WEEKLY PERIODICALS ON THE RIGHT OF THE SCREEN (PDF FILES)TO DOWNLOAD FILES. Look for other issues of the Weekly Register within this website. The Weekly Register, also known as Niles Weekly Register, was a weekly periodical edited by Hezekiah Niles (1777-1839) and published in Baltimore Maryland. Volumes of interest were published between 1811 (Vol. 1, No. 1, September 7, 1811) to 1814 (Vol. 5, No. 26, February 26, 1814). These volumes focus primarily on 19th century politics and government in the United States of America. Niles edited and published the Weekly Register until 1836, making it one of the most widely-circulated magazines in the United States. The popularity also made Niles into one of the most influential journalists of his day. Devoted primarily to politics, Niles' Weekly Register is considered an important source for the history of the period. The Register also recorded current economics, technology, science, medicine, geography, archaeology, the weather, and stories of human interest. Call Number: SPCL PER JK 1 N52

The Weekly Register - September 1811 and Index

Issues for the September 1811 Weekly Register newspaper (Baltimore, Maryland) are divided as follows: September 7th, pages 1-16 September 14th, pages 17-32 September 21st, pages 33-48 September 28th, pages 49-72 PLEASE CLICK ON THE WEEKLY PERIODICALS ON THE RIGHT OF THE SCREEN (PDF FILES)TO DOWNLOAD FILES. Look for other issues of the Weekly Register within this website. The Weekly Register, also known as Niles Weekly Register, was a weekly periodical edited by Hezekiah Niles (1777-1839) and published in Baltimore Maryland. Volumes of interest were published between 1811 (Vol. 1, No. 1, September 7, 1811) to 1814 (Vol. 5, No. 26, February 26, 1814). These volumes focus primarily on 19th century politics and government in the United States of America. Niles edited and published the Weekly Register until 1836, making it one of the most widely-circulated magazines in the United States. The popularity also made Niles into one of the most influential journalists of his day. Devoted primarily to politics, Niles' Weekly Register is considered an important source for the history of the period. The Register also recorded current economics, technology, science, medicine, geography, archaeology, the weather, and stories of human interest. Call Number: SPCL PER JK 1 N52