Validity and Responsiveness of the Portable Warrior Test of Tactical Agility After Rehabilitation in Service Members With Mild Traumatic Brain Injury.

Objective: The Portable Warrior Test of Tactical Agility (POWAR-TOTAL) is a performance-based test designed to assess active-duty service members diagnosed with mild traumatic brain injuries (mTBIs) and could potentially inform return to duty decisions. To examine the validity and responsiveness of the POWAR-TOTAL measure, this study collected self-reported and performance measures by active-duty service members before and after an episode of physical therapist care.

Methods: Seventy-four individuals, enrolled in care for mTBI symptoms at 1 of 2 concussion specialty Intrepid Spirit Centers, were examined the week that they initiated physical therapy with the intention to return to active duty.

Insulin Receptor Substrate Adaptor Proteins Mediate Prognostic Gene Expression Profiles in Breast Cancer.

Therapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins.

Amplified in Breast Cancer Regulates Transcription and Translation in Breast Cancer Cells.

Background: Control of mRNA translation is fundamentally altered in cancer. Insulin-like growth factor-I (IGF-I) signaling regulates key translation mediators to modulate protein synthesis (e.g.

Role of the nuclear receptor coactivator AIB1-Delta4 splice variant in the control of gene transcription.

The oncogene amplified in breast cancer 1 (AIB1) is a nuclear receptor coactivator that plays a major role in the progression of various cancers. We previously identified a splice variant of AIB1 called AIB1-Δ4 that is overexpressed in breast cancer. Using mass spectrometry, we define the translation initiation of AIB1-Δ4 at Met(224) of the full-length AIB1 sequence and have raised an antibody to a peptide representing the acetylated N terminus.

Tyrosine phosphorylation of the nuclear receptor coactivator AIB1/SRC-3 is enhanced by Abl kinase and is required for its activity in cancer cells.

Overexpression and activation of the steroid receptor coactivator amplified in breast cancer 1 (AIB1)/steroid receptor coactivator-3 (SRC-3) have been shown to have a critical role in oncogenesis and are required for both steroid and growth factor signaling in epithelial tumors. Here, we report a new mechanism for activation of SRC coactivators. We demonstrate regulated tyrosine phosphorylation of AIB1/SRC-3 at a C-terminal tyrosine residue (Y1357) that is phosphorylated after insulin-like growth factor 1, epidermal growth factor, or estrogen treatment of breast cancer cells.

E6AP mediates regulated proteasomal degradation of the nuclear receptor coactivator amplified in breast cancer 1 in immortalized cells.

The steroid receptor coactivator oncogene, amplified in breast cancer 1 (AIB1; also known as ACTR/RAC-3/TRAM-1/SRC-3/p/CIP), is amplified and overexpressed in a variety of epithelial tumors. AIB1 has been reported to have roles in both steroid-dependent and steroid-independent transcription during tumor progression. In this report, we describe that the cellular levels of AIB1 are controlled through regulated proteasomal degradation.

Overexpression of an N-terminally truncated isoform of the nuclear receptor coactivator amplified in breast cancer 1 leads to altered proliferation of mammary epithelial cells in transgenic mice.

Amplified in breast cancer 1 (AIB1, also known as ACTR, SRC-3, RAC-3, TRAM-1, p/CIP) is a member of the p160 nuclear receptor coactivator family involved in transcriptional regulation of genes activated through steroid receptors, such as estrogen receptor alpha (ER(alpha)). The AIB1 gene and a more active N-terminally deleted isoform (AIB1-Delta3) are overexpressed in breast cancer. To determine the role of AIB1-Delta3 in breast cancer pathogenesis, we generated transgenic mice with human cytomegalovirus immediate early gene 1 (hCMVIE1) promoter-driven over-expression of human AIB1/ACTR-Delta3 (CMVAIB1/ACTR-Delta3 mice).

Impact of the nuclear receptor coactivator AIB1 isoform AIB1-Delta3 on estrogenic ligands with different intrinsic activity.

The nuclear receptor coactivator amplified in breast cancer 1 (AIB1) and its more active isoform AIB1-Delta3 are overexpressed in breast cancer and preneoplastic breast tissue. However, the impact of these proteins on the transcriptional activity of natural estrogens or selective estrogen receptor modulators (SERMs) has not been determined. Here we show that AIB1-Delta3 causes a significant increase in the efficacy of 17beta-estradiol at both estrogen receptor-alpha (ER-alpha) and ER-beta in ovarian, breast and endometrial cancer cell lines.