Telomere length and replicative aging in human vascular tissues.

Because repeated injury of the endothelium and subsequent turnover of intimal and medial cells have been implicated in atherosclerosis, we examined telomere length, a marker of somatic cell turnover, in cells from these tissues. Telomere lengths were assessed by Southern analysis of terminal restriction fragments (TRFs) generated by HinfI/Rsa I digestion of human genomic DNA. Mean TRF length decreased as a function of population doublings in human endothelial cell cultures from umbilical veins, iliac arteries, and iliac veins. When endothelial cells were examined for mean TRF length as a function of donor age, there was a significantly greater rate of decrease for cells from iliac arteries than from iliac veins (102 bp/yr vs. 47 bp/yr, respectively, P < 0.05), consistent with higher hemodynamic stress and increased cell turnover in arteries. Moreover, the rate of telomere loss as a function of donor age was greater in the intimal DNA of iliac arteries compared to that of the internal thoracic arteries (147 bp/yr vs. 87 bp/yr, respectively, P < 0.05), a region of the arterial tree subject to less hemodynamic stress. This indicates that the effect is not tissue specific. DNA from the medial tissue of the iliac and internal thoracic arteries showed no significant difference in the rates of decrease, suggesting that chronic stress leading to cellular senescence is more pronounced in the intima than in the media. These observations extend the use of telomere size as a marker for the replicative history of cells and are consistent with a role for focal replicative senescence in cardiovascular diseases.

Manuscript copy of the book of Harvard, 1767

Handwritten copy of the Book of Harvard written on one large sheet of paper and signed Boston, January 10th, 1767.

Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study

A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.

Rackham Educational Memorial Building, Detroit, erected 1941

Harley & Ellington, architects. W.E. Wood Co., contractor. Built from July 1940 to January 1942. Built jointly for the Engineering Society of Detroit and the University as an Extension Service facility in Detroit. Funded by the Horace H. and Mary A. Rackham Fund. Sculptures on exterior by Marshall Fredericks.

Administration Building

Harley, Ellington & Day, architects. Occupied in December 1948 by business, administrative, and public service departments, the building was designated as the Administrative Building. Exterior features Marshall Frederick's sculpture. In 1967, upon completion of the Fleming Administration Building, this building became the LS&A Building.

Administration Building Rear

Harley, Ellington & Day, architects. Occupied in December 1948 by business, administrative, and public service departments, the building was designated as the Administrative Building. Exterior features Marshall Frederick's sculpture. In 1967, upon completion of the Fleming Administration Building, this building became the LS&A Building.

Administration Building Rear

Harley, Ellington & Day, architects. Occupied in December 1948 by business, administrative, and public service departments, the building was designated as the Administrative Building. Exterior features Marshall Frederick's sculpture. In 1967, upon completion of the Fleming Administration Building, this building became the LS&A Building. Person in image.

Administration Bldg.

Harley, Ellington & Day, architects. Occupied in December 1948 by business, administrative, and public service departments, the building was designated as the Administrative Building. Exterior features Marshall Frederick's sculpture. In 1967, upon completion of the Fleming Administration Building, this building became the LS&A Building.

Administration Building

Harley, Ellington & Day, architects. Occupied in December 1948 by business, administrative, and public service departments, the building was designated as the Administrative Building. Exterior features Marshall Frederick's sculpture. In 1967, upon completion of the Fleming Administration Building, this building became the LS&A Building.

Administration Building

Harley, Ellington & Day, architects. Occupied in December 1948 by business, administrative, and public service departments, the building was designated as the Administrative Building. Exterior features Marshall Frederick's sculpture. In 1967, upon completion of the Fleming Administration Building, this building became the LS&A Building.

The life and times of Robert Emmet : a lecture delivered in connection with St. Peter's catholic young men's society on Monday 16th Oct. 1869.

Title-page supplied in ms.

Implementation of the language CLEOPATRA : the analysis pass /

Thesis (M. S.)--University of Illinois at Urbana-Champaign.

The Red cross in France,

Mode of access: Internet.

Man in the Arctic : the changing nature of his quest for food and water as related to snow, ice, and permafrost /

"January 1962."