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

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

A near-field scanned microwave probe for spatially localized electrical metrology

We have developed a near-field scanned microwave probe with a sampling volume of approximately 10 micron in diameter, which is the smallest one achieved in near-field microwave microscopy. This volume is defined to confine close to 100 percent of the probe net sampling reactive energy, thus making the response virtually independent on the sample properties outside of this region. The probe is formed by a 4 GHz balanced stripline resonator with a few-micron tip size. It provides non-contact, non-invasive measurement and is uniquely suited for spatially localized electrical metrology applications, e.g. on semiconductor production wafers.Comment: 6 pages, 3 figures, submitted to Appl. Phys. Let

The Role of Oxygen Tension in Penile Erection and Its Relationship to Erectile Dysfunction

The corpus cavernosum of the penis is one of the few vascular beds in which there is a change in oxygen tension with function (blood PO2 25-40mm Hg in the flaccid state, and 90-100mm Hg in the erect state). This change in oxygen tension exposes the components of the corpus cavernosum to a variety of cytokines, humoral, vasoactive, and growth factors which may affect the structure and function of the endothelial cells, smooth muscle cells, neurons and extracellular matrix. Among these cell types, endothelial cells are the first line of defense to blood-borne stress and can affect the underlying smooth muscle via paracrine mechanisms. Impotence is defined as the inability to obtain or sustain an erection sufficient for vaginal penetration and can result from a variety of pathological conditions, vascular disease, endocrine disease, neurological disease, and psychogenic disorders. The penis is a vascular organ and as such is susceptible to the effects of vascular diseases. This review will discuss the basic etiology of erection and vasculogenic erectile dysfunction and explore the role oxygen tension in regulating various cellular and humoral factors as well as trabecular structure and function

An EPIIC Vision to Evolve Project Integration, Innovation, and Collaboration with Broad Impact for How NASA Executes Complex Projects

Evolving Project Integration, Innovation, and Collaboration (EPIIC) is a vision defined to transform the way projects manage information to support real-time decisions, capture best practices and lessons learned, perform assessments, and manage risk across a portfolio of projects. The foundational project management needs for data and information will be revolutionized through innovations on how we manage and access that data, implement configuration control, and certify compliance. The embedded intelligence of new interactive data interfaces integrate technical and programmatic data such that near real time analytics can be accomplished to more efficiently and accurately complete systems engineering and project management tasks. The system-wide data analytics that are integrated into customized data interfaces allows the growing team of engineers and managers required to develop and implement major NASA missions the ability to access authoritative source(s) of system information while greatly reducing the labor required to complete system assessments. This would allow, for example, much of what is accomplished in a scheduled design review to take place as needed, between any team members, at any time. An intelligent data interface that rigorously integrates systems engineering and project management information in near real time can provide substantially greater insight for systems engineers, project managers, and the large diverse teams required to complete a complex project. System engineers, programmatic personnel (those who focus on cost, schedule, and risk), the technical engineering disciplines, and project management can realize immediate benefit from the shared vision described herein. Implementation of the vision also enables significant improvements in the performance of the engineered system being developed