Modified Distillers’ Grain with Solubles Stored for an Extended Period in a Silo Bag Used to Develop Breeding Heifers

Developing breeding heifers were fed two levels of modified distillers’ grains with solubles (MDGS), 17.7 and 32.7% of ration dry matter, in combination with haylages over a 122 day period. Heifers that received 32.7% MDGS in their diet started on feed significantly slower and gained significantly less during the first 46 day period. However, during the remainder of the test the 32.7% MDGS heifers gained significantly faster while consuming less feed than either the controls or the 17.7% MDGS treatment group. After 122 days on trial there were no significant difference in ADG or dry matter conversion between the control or treatment groups, but the 32.7% MDGS group consumed significantly less dry matter per day. There were no significant differences between treatment groups for either synchronized AI pregnancy rate or overall pregnancy rate

"Marker of Self" CD47 on lentiviral vectors decreases macrophage-mediated clearance and increases delivery to SIRPA-expressing lung carcinoma tumors

Lentiviruses infect many cell types and are now widely used for gene delivery in vitro, but in vivo uptake of these foreign vectors by macrophages is a limitation. Lentivectors are produced here from packaging cells that overexpress “Marker of Self” CD47, which inhibits macrophage uptake of cells when prophagocytic factors are also displayed. Single particle analyses show “hCD47-Lenti” display properly oriented human-CD47 for interactions with the macrophage's inhibitory receptor SIRPA. Macrophages derived from human and NOD/SCID/Il2rg−/− (NSG) mice show a SIRPA-dependent decrease in transduction, i.e., transgene expression, by hCD47-Lenti compared to control Lenti. Consistent with known “Self” signaling pathways, macrophage transduction by control Lenti is decreased by drug inhibition of Myosin-II to the same levels as hCD47-Lenti. In contrast, human lung carcinoma cells express SIRPA and use it to enhance transduction by hCD47-Lenti- as illustrated by more efficient gene deletion using CRISPR/Cas9. Intravenous injection of hCD47-Lenti into NSG mice shows hCD47 prolongs circulation, unless a blocking anti-SIRPA is preinjected. In vivo transduction of spleen and liver macrophages also decreases for hCD47-Lenti while transduction of lung carcinoma xenografts increases. hCD47 could be useful when macrophage uptake is limiting on other viral vectors that are emerging in cancer treatments (e.g., Measles glycoprotein-pseudotyped lentivectors) and also in targeting various SIRPA-expressing tumors such as glioblastomas

Probing the orientation of electrostatically immobilized cytochrome C by time of flight secondary ion mass spectrometry and sum frequency generation spectroscopy

By taking advantage of the electron pathway through the heme group in cytochrome c (CytoC) electrochemists have built sensors based upon CytoC immobilized onto metal electrodes. Previous studies have shown that the electron transfer rate through the protein is a function of the position of this heme group with respect to the electrode surface. In this study a detailed examination of CytoC orientation when electrostatically immobilized onto both amine (NH₃⁺) and carboxyl (COO⁻) functionalized gold is presented. Protein coverage, on both surfaces, was monitored by the change in the atomic % N, as determined by x-ray photoelectron spectroscopy. Spectral features within the in situ sum frequency generation vibrational spectra, acquired for the protein interacting with positively and negatively charged surfaces, indicates that these electrostatic interactions do induce the protein into a well ordered film. Time of flight secondary ion mass spectrometry data demonstrated a clear separation between the two samples based on the intensity differences of secondary ions stemming from amino acids located asymmetrically within CytoC (cysteine: C₂H₆NS⁺; glutamic acid: C₄H₆NO⁺ and C₄H₈NO₂⁺; leucine: C₅H₁₂N⁺). For a more quantitative examination of orientation, we developed a ratio comparing the sum of the intensities of secondary-ions stemming from the amino acid residues at either end of the protein. The 50 % increase in this ratio, observed between the protein covered NH₃⁺ and COO⁻ substrates, indicates opposite orientations of the CytoC on the two different surfaces

The Lantern Vol. 64, No. 2, Spring 1997

• Year\u27s End, with Resolutions • Addicted • Muerte, Carlos • Motions • At the Wyeth Gallery • Between Contexts • I\u27m Allowed (and More Nonsense) • Wall and Piece • Timekeeper\u27s Workspace • The Process • Second Sex: A Portrait of the Artist as a Woman • On the Side of the Road • Joe • To Matthew Arnold • A Deep Sleep on Hydrocodone • Madness of a Night • Return • The Sudden Grave • A Farce • Twists of Fur • Ambiguity • The Odor of Continuums • My Father\u27s Daughter • The Meaning of Life • I Aim to Tell • Nobody\u27s Fanhttps://digitalcommons.ursinus.edu/lantern/1150/thumbnail.jp

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease