The effects of moderate aerobic exercise and satyanda yoga on long-term stress, selected cognitive and somatic measures, and learning of a motorskill in response to an acute stressor

The purpose of this investigation was to compare the effects of a 10 week training program of moderate aerobic exercise and satyanda yoga on long-term stress, selected cognitive and somatic measures, and learning a motor skill in response to an acute stressor. The subjects were 44 female (mean age = 19.5yrs) undergraduate students from the University of Wollongong who were considered to be of below average fitness and had no formal stress management experience. All subjects based on their scores on the Jenkins Activity Survey were categorised as Type B. Subjects were randomly assigned to one of four groups: (1) a moderate aerobic exercise group in which subjects participated in a 10-week fitness program consisting of weight training and aerobic/floor stations; (2) a group which practised 10 weeks of satyanda yoga techniques; (3) a placebo group which met once per week for 10 weeks to attend weekly lunch time musical performances; and (4) a no stress control group which underwent initial testing without being exposed to the acute stressor, prior to and at the end of a 10 week period

FOXD3 Regulates VISTA Expression in Melanoma.

Immune checkpoint inhibitors have improved patient survival in melanoma, but the innate resistance of many patients necessitates the investigation of alternative immune targets. Many immune checkpoint proteins lack proper characterization, including V-domain Ig suppressor of T cell activation (VISTA). VISTA expression on immune cells can suppress T cell activity; however, few studies have investigated its expression and regulation in cancer cells. In this study, we observe that VISTA is expressed in melanoma patient samples and cell lines. Tumor cell-specific expression of VISTA promotes tumor onset in vivo, associated with increased intratumoral T regulatory cells, and enhanced PDL-1 expression on tumor-infiltrating macrophages. VISTA transcript levels are regulated by the stemness factor Forkhead box D3 (FOXD3). BRAF inhibition upregulates FOXD3 and reduces VISTA expression. Overall, this study demonstrates melanoma cell expression of VISTA and its regulation by FOXD3, contributing to the rationale for therapeutic strategies that combine targeted inhibitors with immune checkpoint blockade

PARP-1 regulates DNA repair factor availability.

PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity. Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted E2F1-mediated induction of DNA repair factors involved in homologous recombination (HR). Conversely, PARP-1 inhibition reduced HR factor availability and thus acted to induce or enhance BRCA-ness . These observations bring new understanding of PARP-1 function in cancer and have significant ramifications on predicting PARP-1 inhibitor function in the clinical setting

Structure-Based Screen Identifies a Potent Small Molecule Inhibitor of Stat5a/b with Therapeutic Potential for Prostate Cancer and Chronic Myeloid Leukemia.

Bypassing tyrosine kinases responsible for Stat5a/b phosphorylation would be advantageous for therapy development for Stat5a/b-regulated cancers. Here, we sought to identify small molecule inhibitors of Stat5a/b for lead optimization and therapy development for prostate cancer and Bcr-Abl-driven leukemias. In silico screening of chemical structure databases combined with medicinal chemistry was used for identification of a panel of small molecule inhibitors to block SH2 domain-mediated docking of Stat5a/b to the receptor-kinase complex and subsequent phosphorylation and dimerization. We tested the efficacy of the lead compound IST5-002 in experimental models and patient samples of two known Stat5a/b-driven cancers, prostate cancer and chronic myeloid leukemia (CML). The lead compound inhibitor of Stat5-002 (IST5-002) prevented both Jak2 and Bcr-Abl-mediated phosphorylation and dimerization of Stat5a/b, and selectively inhibited transcriptional activity of Stat5a (IC50 = 1.5μmol/L) and Stat5b (IC50 = 3.5 μmol/L). IST5-002 suppressed nuclear translocation of Stat5a/b, binding to DNA and Stat5a/b target gene expression. IST5-002 induced extensive apoptosis of prostate cancer cells, impaired growth of prostate cancer xenograft tumors, and induced cell death in patient-derived prostate cancers when tested ex vivo in explant organ cultures. Importantly, IST5-002 induced robust apoptotic death not only of imatinib-sensitive but also of imatinib-resistant CML cell lines and primary CML cells from patients. IST5-002 provides a lead structure for further chemical modifications for clinical development for Stat5a/b-driven solid tumors and hematologic malignancies

Red Waters of Myrionecta rubra are Biogeochemical Hotspots for the Columbia River Estuary with Impacts on Primary/Secondary Productions and Nutrient Cycles

The localized impact of blooms of the mixotrophic ciliate Myrionecta rubra in the Columbia River estuary during 2007-2010 was evaluated with biogeochemical, light microscopy, physiological, and molecular data. M. rubra affected surrounding estuarine nutrient cycles, as indicated by high and low concentrations of organic nutrients and inorganic nitrogen, respectively, associated with red waters. M. rubra blooms also altered the energy transfer pattern in patches of the estuarine water that contain the ciliate by creating areas characterized by high primary production and elevated levels of fresh autochthonous particulate organic matter, therefore shifting the trophic status in emergent red water areas of the estuary from net heterotrophy towards autotrophy. The pelagic estuarine bacterial community structure was unaffected by M. rubra abundance, but red waters of the ciliate do offer a possible link between autotrophic and heterotrophic processes since they were associated with elevated dissolved organic matter and showed a tendency for enhanced microbial secondary production. Taken together, these findings suggest that M. rubra red waters are biogeochemical hotspots of the Columbia River estuary.Keywords: Myrionecta rubra, Biogeochemical cycles, Red waters, Mesodinium rubrum, Columbia River estuar

Signal Transmission in the Auditory System

Contains table of contents for Section 3, an introduction, and reports on seven research projects.National Institutes of Health Grant 5 R01 DC00194National Institutes of Health Grant P01 DC00119National Institutes of Health Grant F32 DC00073National Institutes of Health Grant 5 R01 DC00473National Institutes of Health Grant 2 R01 DC00238National Institutes of Health Grant 2 R01 DC00235National Institutes of Health Grant 5 P01 DC00361National Institutes of Health Grant T32 DC00006Whitaker Health Sciences Fun

The αvβ6 integrin in cancer cell-derived small extracellular vesicles enhances angiogenesis.

Prostate cancer (PrCa) cells crosstalk with the tumour microenvironment by releasing small extracellular vesicles (sEVs). sEVs, as well as large extracellular vesicles (LEVs), isolated via iodixanol density gradients from PrCa cell culture media, express the epithelial-specific αvβ6 integrin, which is known to be induced in cancer. In this study, we show sEV-mediated protein transfer of αvβ6 integrin to microvascular endothelial cells (human microvascular endothelial cells 1 - HMEC1) and demonstrate tha

Signal Transmission in the Auditory System

Contains table of contents for Section 3, an introduction and reports on six research projects.National Institutes of Health Grant R01-DC-00194National Institutes of Health Contract P01-DC-00119National Institutes of Health Fellowship F32-DC00073National Institutes of Health Grant R01-DC00238National Institutes of Health Grant R01-DC00473National Institutes of Health Grant T32-DC00006National Institutes of Health Grant T32-DC00038National Institutes of Health Contract P01-DC00361National Institutes of Health Grant R01-DC00235National Institutes of Health Contract N01-DC2240

Signal Transmission in the Auditory System

Contains table of contents for Section 3, an introduction and reports on six research projects.National Institutes of Health Grant R01-DC-00194-11National Institutes of Health Grant P01-DC00119 Sub-Project 1National Institutes of Health Grant F32-DC00073-2National Institutes of Health Contract P01-DC00119National Institutes of Health Grant R01-DC00238National Institutes of Health Gramt R01-DC00473National Institutes of Health Grant P01-DC00119National Institutes of Health Grant T32-DC00038PNational Institutes of Health Grant P01-DC00361National Institutes of Health Grant 2RO1 DC00235National Institutes of Health Contract NO1-DC2-240

Signal Transmission in the Auditory System

Contains table of contents for Section 3, an introduction and reports on six research projects.Health Sciences FundNational Institutes of Health Grant 5 R01 DC00194National Institutes of Health Grant 8 P01 DC00119National Institutes of Health Grant 5 R01 DC00473National Institutes of Health Grant 5 R01 DC00238National Institutes of Health Grant 5 T32 DC00006National Institutes of Health Grant 5 P01 DC00361National Institutes of Health Grant 5 R01 DC00235Peoples Republic of China FellowshipUnisys Corporation Doctoral FellowshipWhitaker Health Sciences Fellowshi