108 research outputs found

    Phorbol 12,13-Dibutyrate-Induced, Protein Kinase C-Mediated Contraction of Rabbit Bladder Smooth Muscle

    Get PDF
    Contraction of bladder smooth muscle is predominantly initiated by M3 muscarinic receptor-mediated activation of the Gq/11-phospholipase C β-protein kinase C (PKC) and the G12/13-RhoGEF-Rho kinase (ROCK) pathways. However, these pathways and their downstream effectors are not well understood in bladder smooth muscle. We used phorbol 12,13-dibutyrate (PDBu), and 1,2-dioctanoyl-sn-glycerol (DOG), activators of PKC, in this investigation. We were interested in dissecting the role(s) of PKC and to clarify the signaling pathways in bladder smooth muscle contraction, especially the potential cross-talk with ROCK and their downstream effectors in regulating myosin light chain phosphatase activity and force. To achieve this goal, the study was performed in the presence or absence of the PKC inhibitor bisindolylmaleimide-1 (Bis) or the ROCK inhibitor H-1152. Phosphorylation levels of Thr38-CPI-17 and Thr696/Thr850 myosin phosphatase target subunit (MYPT1) were measured during PDBu or DOG stimulation using site specific antibodies. PDBu-induced contraction in bladder smooth muscle involved both activation of PKC and PKC-dependent activation of ROCK. CPI-17 as a major downstream effector, is phosphorylated by PKC and ROCK during PDBu and DOG stimulation. Our results suggest that Thr696 and Thr850-MYPT1 phosphorylation are not involved in the regulation of a PDBu-induced contraction. The results also demonstrate that bladder smooth muscle contains a constitutively active isoform of ROCK that may play an important role in the regulation of bladder smooth muscle basal tone. Together with the results from our previous study, we developed a working model to describe the complex signaling pathways that regulate contraction of bladder smooth muscle

    Adequacy of nutritional intake among older men living in Sydney, Australia: findings from the Concord Health and Ageing in Men Project (CHAMP)

    Get PDF
    Previous research shows that older men tend to have lower nutritional intakes and higher risk of under-nutrition compared with younger men. The objectives of this study were to describe energy and nutrient intakes, assess nutritional risk and investigate factors associated with poor intake of energy and key nutrients in community-dwelling men aged 75 years participating in the Concord Health and Ageing in Men Project - a longitudinal cohort study on older men in Sydney, Australia. A total of 794 men (mean age 81.4 years) had a detailed diet history interview, which was carried out by a dietitian. Dietary adequacy was assessed by comparing median intakes with nutrient reference values (NRV): estimated average requirement, adequate intake or upper level of intake. Attainment of NRV of total energy and key nutrients in older age (protein, Fe, Zn, riboflavin, Ca and vitamin D) was incorporated into a "key nutrients" variable dichotomised as "good" (5) or "poor" (4). Using logistic regression modelling, we examined associations between key nutrients with factors known to affect food intake. Median energy intake was 8728 kJ (P5=5762 kJ, P95=12 303 kJ), and mean BMI was 27.7 (sd 4.0) kg/m(2). Men met their NRV for most nutrients. However, only 1 % of men met their NRV for vitamin D, only 19 % for Ca, only 30 % for K and only 33 % for dietary fibre. Multivariate logistic regression analysis showed that only country of birth was significantly associated with poor nutritional intake. Dietary intakes were adequate for most nutrients; however, only half of the participants met the NRV of 5 key nutrients

    Signal Transduction Involving the Dmp1 Transcription Factor and its Alteration in Human Cancer

    Get PDF
    Dmp1 (cyclin D-interacting myb-like protein 1; also called Dmtf1) is a transcription factor that has been isolated in a yeast two-hybrid screen through its binding property to cyclin D2. Dmp1 directly binds to and activates the Arf promoter and induces Arf-p53-dependent cell cycle arrest in primary cells. D-type cyclins usually inhibit Dmp1-mediated transcription in a Cdk-independent fashion; however, Dmp1 shows synergistic effects with D-cyclins on the Arf promoter. Ras or Myc oncogene-induced tumor formation is accelerated in both Dmp1+/− and Dmp1−/− mice with no significant differences between Dmp1+/− and Dmp1−/−. Thus, Dmp1 is haplo-insufficient for tumor suppression. Tumors from Dmp1−/− or Dmp1+/− mice often retain wild-type Arf and p53, suggesting that Dmp1 is a physiological regulator of the Arf-p53 pathway. The Dmp1 promoter is activated by oncogenic Ras-Raf signaling, while it is repressed by physiological mitogenic stimuli, overexpression of E2F proteins, and genotoxic stimuli mediated by NF-κB. The human DMP1 gene (hDMP1) is located on chromosome 7q21 and is hemizygously deleted in approximately 40% of human lung cancers, especially those that retain normal INK4a/ARF and P53 loci. Thus, hDMP1 is clearly involved in human carcinogenesis, and tumors with hDMP1 deletion may constitute a discrete disease entity

    Pennsylvania Folklife Vol. 31, No. 3

    Get PDF
    • Jamison City • Domestic Architecture in Lancaster County • Conversation with Marguerite de Angeli • Who Put the Turnip on the Grave? • Pennsylfawnisch Deitsch un Pfalzer: Dialect Comparisons Old and New • John Philip Boehm: Pioneer Pennsylvania Pastor • The Search for our German Ancestors • Aldes un Neieshttps://digitalcommons.ursinus.edu/pafolklifemag/1095/thumbnail.jp

    Identifying invasive species threats, pathways, and impacts to improve biosecurity

    Get PDF
    Managing invasive species with prevention and early-detection strategies can avert severe ecological and economic impacts. Horizon scanning, an evidence-based process combining risk screening and consensus building to identify threats, has become a valuable tool for prioritizing invasive species management and prevention. We assembled a working group of experts from academic, government, and nonprofit agencies and organizations, and conducted a multi-taxa horizon scan for Florida, USA, the first of its kind in North America. Our primary objectives were to identify high-risk species and their introduction pathways, to detail the magnitude and mechanism of potential impacts, and, more broadly, to demonstrate the utility of horizon scanning. As a means to facilitate future horizon scans, we document the process used to generate the list of taxa for screening. We evaluated 460 taxa for their potential to arrive, establish, and cause negative ecological and socioeconomic impacts, and identified 40 potential invaders, including alewife, zebra mussel, crab-eating macaque, and red swamp crayfish. Vertebrates and aquatic invertebrates posed the greatest invasion threat, over half of the high-risk taxa were omnivores, and there was high confidence in the scoring of high-risk taxa. Common arrival pathways were ballast water, biofouling of vessels, and escape from the pet/aquarium/horticulture trade. Competition, predation, and damage to agriculture/forestry/aquaculture were common impact mechanisms. We recommend full risk analysis for the high-risk taxa; increased surveillance at Florida's ports, state borders, and high-risk pathways; and periodic review and revision of the list. Few horizon scans detail the comprehensive methodology (including list-building), certainty estimates for all scoring categories and the final score, detailed pathways, and the magnitude and mechanism of impact. Providing this information can further inform prevention efforts and can be efficiently replicated in other regions. Moreover, harmonizing methodology can facilitate data sharing and enhance interpretation of results for stakeholders and the general public.</p
    corecore