Mural cells in the microvasculature of visceral organs develop spontaneous Ca transients. However, the mechanisms underlying the integration of these Ca transients within a microvascular unit remain to be clarified. In the present study, the origin of spontaneous Ca transients and their propagation in the bladder suburothelial microvasculature were explored. Cal-520 fluorescence Ca imaging and immunohistochemistry were carried out on mural cells using mice expressing red fluorescent protein (DsRed) under control of the NG2 promotor. NG2(+) pericytes in both pre-capillary arterioles (PCAs) and capillaries developed synchronous spontaneous Ca transients. By contrast, although NG2-DsRed also labelled arteriolar smooth muscle cells, these cells remained quiescent. Both NG2(+) pericytes in post-capillary venules (PCVs) and NG2(-) venular pericytes exhibited propagated Ca transients. L-type voltage-dependent Ca channel (LVDCC) blockade with nifedipine prevented Ca transients or disrupted their synchrony in PCA, PCV and venular pericytes without dis-synchronizing Ca transients in capillary pericytes. Blockade of gap junctions with carbenoxolone or Ca -activated chloride channels (CaCCs) with 4,4'-diisothiocyanato-2,2'-stilbenedisulphonic acid disodium salt prevented Ca transients in PCA and venular pericytes and disrupted the synchrony of Ca transients in capillary and PCV pericytes. Spontaneous Ca transients in pericytes of all microvascular segments were abolished or suppressed by cyclopiazonic acid, caffeine or tetracaine. The synchrony of Ca transients in capillary pericytes arising from spontaneous Ca release from the sarco- and endoplasmic reticulum appears to rely exclusively on CaCC activation, whereas subsequent LVDCC activation is required for the synchrony of Ca transients in pericytes of other microvascular segments. Capillary pericytes may drive spontaneous activity in the suburothelial microvascular unit to facilitate capillary perfusion.
Abstract. We review the current state of tabletop extreme ultraviolet (XUV) sources based on high harmonic generation (HHG) in femtosecond enhancement cavities (fsEC). Recent developments have enabled generation of high photon flux (10 14 photons/sec) in the XUV, at high repetition rates (>50 MHz) and spanning the spectral region from 40 nm -120 nm. This level of performance has enabled precision spectroscopy with XUV frequency combs and promises further applications in XUV spectroscopic and photoemission studies. We discuss the theory of operation and experimental details of the fsEC and XUV generation based on HHG, including current technical challenges to increasing the photon flux and maximum photon energy produced by this type of system. Current and future applications for these sources are also discussed.
Plain English summary Involving consumers and community members in the research process is an important step towards developing and delivering effective, person-centered health care. The National Health and Medical Research Council have provided recommendations for involving consumers and community members in research; however, definitive actions to implement these are not well defined. To address this, an established research centre in Melbourne, Australia, has developed a consumer and community involvement framework to incorporate the national recommendations into their research program. This paper describes the framework the research centre has employed, in the hope that other researchers can adapt this approach and learnings to their own research practices. The framework described in this paper aims to foster partnerships between consumers, community members and researchers, and in doing so, encourages consumers to be actively involved in research to help improve future outcomes for those living with musculoskeletal conditions. Simultaneously, the framework encourages researchers to value the consumer voice in their research to ensure they yield meaningful research outcomes for those living with musculoskeletal conditions. Abstract Background The value of involving consumers and community members in every stage of the research process is gaining recognition as an important consideration in the wider research landscape. The National Health and Medical Research Council (NHMRC) has provided general recommendations for involving consumers and community members in research, although the translation of these recommendations into tangible actions has not yet been well defined. In light of these recommendations, many research institutions are now seeking to incorporate the voices of consumers and community members in their research practices. Methods The consumer and community involvement framework described in this paper incorporates the NHMRC’s recommendations to produce a four-tiered model where consumer participants nominate their level of involvement depending on their research interests and preferred level of commitment. In ascending order, the tiers are: Consumer Subscriber, Document Reviewer, Research Buddy and Consumer Advocate. The success of this framework depends upon the implementation of effective governance and access to appropriate infrastructure. A Consumer and Community Advisory Group and a designated Consumer and Community Liaison Officer will take responsibility for ensuring appropriate interactions between consumers, researchers, and the research center’s executive team. The framework aims to apply suitable support structures in place to manage expectations and minimize barriers to effective involvement, whilst ensuring that consumer contributions are appropriately valued and incorporated in the research. Discussion Involving consumers and community members in the research process is an important step towards developing and delivering effective, person-centered health care. While consumer and community involvement offer researchers invaluable perspectives on their research program, it provides an opportunity for consumers and community members to be actively involved in health research and improve the health and wellbeing for those living with health conditions.
Background and purpose: Changes in smooth muscle tone of the prostate gland are involved in aetiology of symptomatic prostatic hyperplasia, however the control mechanisms of prostatic smooth muscle are not well understood. Here, we have examined the role of internal Ca 2+ compartments in regulating slow wave activity in the guinea pig prostate. Experimental approach: Standard intracellular membrane potential recording techniques were used. Key results: The majority (89%) of impaled cells displayed 'slow wave' activity. Cyclopiazonic acid (10 mmol·L -1 ) transiently depolarized (3-9 mV) the membrane potential of the prostatic stroma and transiently increased slow wave frequency. Thereafter, slow wave frequency slowly decreased over 20-30 min. Ryanodine transiently increased slow wave frequency, although after 30 min exposure slow wave frequency and time course returned to near control values. Caffeine (1 mmol·L -1 ) reduced slow wave frequency, accompanied by membrane depolarization of about 8 mV. Blockade of inositol trisphosphate receptor (IP3R)-mediated Ca 2+ release with 2-aminoethoxy-diphenylborate (60 mmol·L -1 ) or Xestospongin C (3 mmol·L -1 ) or inhibiting phospholipase C and IP3 formation using U73122 (5 mmol·L -1 ) or neomycin (1 and 4 mmol·L -1 ) reduced slow wave frequency, amplitude and duration. The mitochondrial uncouplers, p-trifluoromethoxy carbonyl cyanide phenyl hydrazone (1-10 mmol·L -1 ), carbonyl cyanide m-chlorophenylhydrazone (1-3 mmol·L -1 ) or rotenone (10 mmol·L -1 ), depolarized the membrane (8-10 mV) before abolishing electrical activity. Conclusion and implications:These results suggest that slow wave activity was dependent on the cyclical release of Ca 2+ from IP3-controlled internal stores and mitochondria. This implies that intracellular compartments were essential in the initiation and/or maintenance of the regenerative contractile activity in the guinea pig prostate gland.
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