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331.
Zannatul Ferdous Muhammad Anwar Qureshi Petrilla Jayaprakash Khatija Parekh Annie John Murat Oz Haider Raza Halina Dobrzynski Thomas Edward Adrian Frank Christopher Howarth 《PloS one》2016,11(4)
BackgroundExperiments in isolated perfused heart have shown that heart rate is lower and sinoatrial node (SAN) action potential duration is longer in streptozotocin (STZ)–induced diabetic rat compared to controls. In sino-atrial preparations the pacemaker cycle length and sino-atrial conduction time are prolonged in STZ heart. To further clarify the molecular basis of electrical disturbances in the diabetic heart the profile of mRNA encoding a wide variety of proteins associated with the generation and transmission of electrical activity has been evaluated in the SAN of STZ-induced diabetic rat heart.Conclusions/SignificanceCollectively, this study has demonstrated differences in the profile of mRNA encoding a variety of proteins that are associated with the generation, conduction and regulation of electrical signals in the SAN of STZ-induced diabetic rat heart. Data from this study will provide a basis for a substantial range of future studies to investigate whether these changes in mRNA translate into changes in electrophysiological function. 相似文献
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Guangyuan Li Isaac N. Hayward Brittany R. Jenkins Heather M. Rothfuss Coleman H. Young Marja T. Nevalainen Aaron Muth Paul R. Thompson Amy M. Navratil Brian D. Cherrington 《PloS one》2016,11(1)
Peptidylarginine deiminases (PADs) post-translationally convert arginine into neutral citrulline residues. Our past work shows that PADs are expressed in the canine and murine mammary glands; however, the mechanisms regulating PAD expression and the function of citrullination in the normal mammary gland are unclear. Therefore, the first objective herein was to investigate regulation of PAD expression in mammary epithelial cells. We first examined PAD levels in CID-9 cells, which were derived from the mammary gland of mid-pregnant mice. PAD3 expression is significantly higher than all other PAD isoforms and mediates protein citrullination in CID-9 cells. We next hypothesized that prolactin regulates PAD3 expression. To test this, CID-9 cells were stimulated with 5 μg/mL of prolactin for 48 hours which significantly increases PAD3 mRNA and protein expression. Use of a JAK2 inhibitor and a dominant negative (DN)-STAT5 adenovirus indicate that prolactin stimulation of PAD3 expression is mediated by the JAK2/STAT5 signaling pathway in CID-9 cells. In addition, the human PAD3 gene promoter is prolactin responsive in CID-9 cells. Our second objective was to investigate the expression and activity of PAD3 in the lactating mouse mammary gland. PAD3 expression in the mammary gland is highest on lactation day 9 and coincident with citrullinated proteins such as histones. Use of the PAD3 specific inhibitor, Cl4-amidine, indicates that PAD3, in part, can citrullinate proteins in L9 mammary glands. Collectively, our results show that upregulation of PAD3 is mediated by prolactin induction of the JAK2/STAT5 signaling pathway, and that PAD3 appears to citrullinate proteins during lactation. 相似文献
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A scale‐down mimic for mapping the process performance of centrifugation,depth and sterile filtration 下载免费PDF全文
Adrian Joseph Brian Kenty Michael Mollet Kenneth Hwang Steven Rose Stephen Goldrick Jean Bender Suzanne S. Farid Nigel Titchener‐Hooker 《Biotechnology and bioengineering》2016,113(9):1934-1941
In the production of biopharmaceuticals disk‐stack centrifugation is widely used as a harvest step for the removal of cells and cellular debris. Depth filters followed by sterile filters are often then employed to remove residual solids remaining in the centrate. Process development of centrifugation is usually conducted at pilot‐scale so as to mimic the commercial scale equipment but this method requires large quantities of cell culture and significant levels of effort for successful characterization. A scale‐down approach based upon the use of a shear device and a bench‐top centrifuge has been extended in this work towards a preparative methodology that successfully predicts the performance of the continuous centrifuge and polishing filters. The use of this methodology allows the effects of cell culture conditions and large‐scale centrifugal process parameters on subsequent filtration performance to be assessed at an early stage of process development where material availability is limited. Biotechnol. Bioeng. 2016;113: 1934–1941. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. 相似文献
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Carla Minguet-Parramona Yizhou Wang Adrian Hills Silvere Vialet-Chabrand Howard Griffiths Simon Rogers Tracy Lawson Virgilio L. Lew Michael R. Blatt 《Plant physiology》2016,170(1):33-42
Oscillations in cytosolic-free Ca2+ concentration ([Ca2+]i) have been proposed to encode information that controls stomatal closure. [Ca2+]i oscillations with a period near 10 min were previously shown to be optimal for stomatal closure in Arabidopsis (Arabidopsis thaliana), but the studies offered no insight into their origins or mechanisms of encoding to validate a role in signaling. We have used a proven systems modeling platform to investigate these [Ca2+]i oscillations and analyze their origins in guard cell homeostasis and membrane transport. The model faithfully reproduced differences in stomatal closure as a function of oscillation frequency with an optimum period near 10 min under standard conditions. Analysis showed that this optimum was one of a range of frequencies that accelerated closure, each arising from a balance of transport and the prevailing ion gradients across the plasma membrane and tonoplast. These interactions emerge from the experimentally derived kinetics encoded in the model for each of the relevant transporters, without the need of any additional signaling component. The resulting frequencies are of sufficient duration to permit substantial changes in [Ca2+]i and, with the accompanying oscillations in voltage, drive the K+ and anion efflux for stomatal closure. Thus, the frequency optima arise from emergent interactions of transport across the membrane system of the guard cell. Rather than encoding information for ion flux, these oscillations are a by-product of the transport activities that determine stomatal aperture.Stomata in the leaf epidermis are the main pathway both for CO2 entry for photosynthesis and for foliar water loss by transpiration. Guard cells surround the stomatal pore and regulate the aperture, balancing the often conflicting demands for CO2 and water conservation. Guard cells open and close the pore by expanding and contracting through the uptake and loss, respectively, of osmotic solutes, notably of K+, Cl−, and malate2− (Mal2−; Pandey et al., 2007; Kim et al., 2010; Roelfsema and Hedrich, 2010; Lawson and Blatt, 2014). These transport processes comprise the final effectors of a regulatory network that coordinates transport across the plasma membrane and tonoplast, and maintains the homeostasis of the guard cell. A number of well-defined signals—including light, CO2, drought and the water stress hormone abscisic acid (ABA)—act on this network, altering transport, solute content, turgor and cell volume, and ultimately stomatal aperture.Much research has focused on stomatal closure, underscoring both Ca2+-independent and Ca2+-dependent signaling. Of the latter, elevated cytosolic-free Ca2+ concentration ([Ca2+]i) inactivates inward-rectifying K+ channels (IK,in) to prevent K+ uptake and activates Cl− (anion) channels (ICl) at the plasma membrane to depolarize the membrane and engage K+ efflux through outward-rectifying K+ channels (IK,out; Keller et al., 1989; Blatt et al., 1990; Thiel et al., 1992; Lemtiri-Chlieh and MacRobbie, 1994). ABA, and most likely CO2 (Kim et al., 2010), elevate [Ca2+]i by facilitating Ca2+ entry at the plasma membrane to trigger Ca2+ release from endomembrane stores, a process often described as Ca2+-induced Ca2+ release (Grabov and Blatt, 1998, 1999). The hormone promotes Ca2+ influx by activating Ca2+ channels (ICa) at the plasma membrane, even in isolated membrane patches (Hamilton et al., 2000, 2001), which is linked to reactive oxygen species (Kwak et al., 2003; Wang et al., 2013). In parallel, cADP-ribose and nitric oxide promote endomembrane Ca2+ release and [Ca2+]i elevation (Leckie et al., 1998; Neill et al., 2002; Garcia-Mata et al., 2003; Blatt et al., 2007). Best estimates indicate that endomembrane release accounts for more than 95% of the Ca2+ entering the cytosol to raise [Ca2+]i (Chen et al., 2012; Wang et al., 2012).One feature of stomatal response to ABA, and indeed to a range of stimuli both hormonal as well as external, is its capacity for oscillations both in membrane voltage and [Ca2+]i. Guard cell [Ca2+]i at rest is typically around 100 to 200 nm, as it is in virtually all living cells. In response to ABA, [Ca2+]i can rise above 1 μm—and locally, most likely above 10 μm—often in cyclic transients of tens of seconds to several minutes’ duration in association with oscillations in voltage and stomatal closure (Gradmann et al., 1993; McAinsh et al., 1995; Webb et al., 1996; Grabov and Blatt, 1998, 1999; Staxen et al., 1999; Allen et al., 2001). In principle, cycling in voltage and [Ca2+]i arises as closure is accelerated with a controlled release of K+, Cl−, and Mal2− from the guard cell and is subject to extracellular ion concentrations (Gradmann et al., 1993; Chen et al., 2012). However, it has been proposed that these, and similar oscillations in a variety of plant cell models, serve as physiological signals in their own right (McAinsh et al., 1995; Ehrhardt et al., 1996; Taylor et al., 1996). In support of such a signaling role, experiments designed to impose [Ca2+]i (and voltage) oscillations in guard cells have yielded an optimal frequency for closure with a period near 10 min (Allen et al., 2001). Nonetheless, the studies offer no mechanistic explanation for this optimum that could validate a causal role in signaling, and none has been forthcoming since. Here we address questions of how such optimal frequencies in [Ca2+]i oscillation arise and their relevance for stomatal closure, using quantitative systems analysis of guard cell transport and homeostasis. Our findings indicate that oscillations in voltage and [Ca2+]i, and their optima associated with stomatal closure, are most simply explained as emerging from the interactions between ion transporters that drive stomatal closure. Thus, we conclude that these oscillations do not control, but are a by-product of the transport that determines stomatal aperture. 相似文献
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Adrian Favell 《Ethnic and racial studies》2016,39(13):2352-2360
ABSTRACTA critical review of Alba and Foner's Strangers No More (2015) which focuses on questioning their comparative assimilation of European cases of immigrant integration to the North American, specifically U.S., experience. While this may work in terms of how national immigrant integration has mitigated over time racial discrimination for older, post-colonial migrants, it misrepresents the complex differentiations involved in the super-diversity of recent ‘new’ migrations within and to Europe. In particular, the variety of types and origins of recent migration is lost in their understanding of the U.K. case, with problems linked to their interpretation of data about minorities and foreigners in the country. 相似文献
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Adrian Stencel 《Biology & philosophy》2016,31(5):619-637
If there is a single discipline of science calling the basic concepts of biology into question, it is without doubt microbiology. Indeed, developments in microbiology have recently forced us to rethink such fundamental concepts as the organism, individual, and genome. In this paper I show how microorganisms are changing our understanding of natural aggregations and develop the concept of a Darwinian population to embrace these discoveries. I start by showing that it is hard to set the boundaries of a Darwinian population, and I suggest thinking of a Darwinian population as a relative property of a Darwinian individual. Then I argue, in contrast to the commonly held view, that Darwinian populations are multispecies units, and that in order to accept the multispecies account of Darwinian populations we have to separate fitness from natural selection. Finally, I show how all these ideas provide a theoretical framework leading to a more precise understanding of the ecology of endosymbiosis than is afforded by poetic metaphors such as ‘slavery’. 相似文献