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Grb7 is an adapter protein found to be overexpressed in several breast and other cancer cell types along with ErbB2. Grb7 is normally an interaction partner with focal adhesion kinase and in cancer cells also aberrantly interacts with ErbB2. It is thus implicated in the migratory and proliferative potential of cancer cells. Previous studies have shown that the phage display-derived cyclic nonphosphorylated inhibitor peptide, G7-18NATE, when linked to Penetratin©, is able to interfere with the interaction of Grb7 with its upstream binding partners and to impact on both cell migration and proliferation. Here we report the synthesis of a biotinylated G7-18NATE covalently attached to just the last seven residues of Penetratin© (G7-18NATE-P-Biotin). We demonstrate that this construct is taken up efficiently into MDA-MB-468 breast cancer cells and colocalizes with Grb7 in the cytoplasm. We also used isothermal titration calorimetry to determine the binding affinity of G7-18NATE-P-Biotin to the Grb7-SH2 domain, and showed that it binds with micromolar affinity (Kd= 14.4 µM), similar to the affinity of G7-18NATE (Kd= 35.4 µM). Together this shows that this shorter G7-18NATE-P-Biotin construct is suitable for further studies of the antiproliferative and antimigratory potential of this inhibitor. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 181–188, 2011.

Profile of Charles F. Dolan, chairman and CEO of Cablevision Systems Corp. Pros and cons to Cablevision's informal style of business.

Discusses the legal impact unwired networks are having on the way advertising is sold to television. INSET: Mike Kammerer's unwired work.;President of Independent....

Discusses CBS' `Designing Women,' produced by Linda Bloodworth-Thomason and Harry Thomason for Columbia Pictures Television. The four charming eccentrics on the show have established a loyal following in the urban South. Universal element in the show; Viewer response; Show topics; Regionally flavored television.

We describe a young girl who presented with recurrent episodes of central nervous system (CNS) demyelination mimicking multiple sclerosis. Metabolic evaluations and decreased oxidation of [9,10(n)−3H] palmitate demonstrated defective mitochondrial beta oxidation, but complementation studies of the patient's cells, fused with cell lines with known defects of beta oxidation, failed to identify a known disorder. While progressive CNS demyelination has occurred in patients with defective peroxisomal very long-chain fatty acid oxidation, this is the 1st time it has occurred with defective mitochondrial beta oxidation. This patient appears to represent a novel disorder of beta oxidation producing intermittent demyelination with profound CNS symptoms. Recognition of the defect led to appropriate therapy, which caused marked clinical improvement.

KOKKINOS, P. F., B. F. HURLEY, M. A. SMUTOK, C. FARMER, C. REECE, R. SHULMAN, C. CHARABOGOS, J. PATTERSON, S. WILL, J. DEVANE-BELL, and A. P. GOLDBERG. Strength training does not improve lipoprotein-lipid profiles in men at risk for CHD. Med. Sci. Sports Exerc., Vol. 23, No. 10, pp. 1134–1139, 1991. Sixteen untrained males, age 46 ± 11 yr (X ± SD), were studied to determine the effects of 20 wk of strength training on lipoprotein-lipid profiles and post-heparin lipase activities. All subjects had abnormal lipoprotein-lipid profiles and at least two other risk factors for coronary heart disease (CHD). To control for day-to-day variations in blood lipoprotein levels, baseline values were established by taking at least two blood samples on separate days from the training and control groups. The training program resulted in a 50 increase in upper body strength (P< 0.001) and a 37 increase in lower body strength (P< 0.001) as measured by the one repetition maximum test (1-RM). No changes in the 1-RM test were observed in the control group. There were no significant changes in O2max(34.5 ± 6.4 vs 36.2 ± 7.4 ml.kg-1.min-1or percent fat (25.4 ± 4.2 vs 24.9 ± 4.1) with training. There were also no significant changes in plasma concentrations of triglyceride (193 ± 96 vs 171 ± 101 mg.dl-1), total cholesterol (231 ± 22 vs 210 ± 22 mg.dl-1), and HDL-C (35 ± 6 vs 36 ± 8 mg.dl-1), or LDL-C (139 ± 16 vs 139 ± 21 mg.dl-1). Furthermore, the activities of post-heparin lipoprotein lipase (9 ± 4 vs 13 ± 5 moles.ml-1.h-1) and hepatic lipase (35 ± 10 vs 35 ± 9 moles.ml-1.h-1) did not change with training. These results indicate that strength training does not improve lipoprotein-lipid profiles or alter the lipases that regulate HDL-C and triglyceride metabolism in men who are at risk for CHD.

The effect of two static pre-load levels on isokinetic concentric (CON) and eccentric (ECC) performance of the knee extensors at 90°-s−1was evaluated in 35 healthy subjects. The low pre-load level was 50 N, and the high level was 75 of a maximal voluntary isometric contraction, performed at the start angles of 100 degrees (CON) and 30 degrees (ECC) of knee flexion. A two-way ANOVA with two repeated measures (load and angle) and a Newman-Keuls post hocanalysis were performed to compare the interaction of pre-load and angle at every 5 degrees in the ROM. The differences in average torque, peak torque, and peak torque angle between the pre-load levels were also analyzed with repeated-measures Mests. The high pre-load condition had a significant increase in torque at 99, 95, 90, and 85 degrees concentrically and 31, 35, 40, 45, and 50 degrees eccentrically. In comparing the two pre-load conditions over the whole torque curve, there was a significant difference in average torque values of both CON and ECC, no significant difference in peak torque in either contraction, and a significant shift in peak torque angle with CON contractions only.