Selective involvement of serum response factor in pressure-induced myogenic tone in resistance arteries

OBJECTIVE: In resistance arteries, diameter adjustment in response to pressure changes depends on the vascular cytoskeleton integrity. Serum response factor (SRF) is a dispensable transcription factor for cellular growth, but its role remains unknown in resistance arteries. We hypothesized that SRF is required for appropriate microvascular contraction. METHODS AND RESULTS: We used mice in which SRF was specifically deleted in smooth muscle or endothelial cells, and their control. Myogenic tone and pharmacological contraction was determined in resistance arteries. mRNA and protein expression were assessed by quantitative real-time PCR (qRT-PCR) and Western blot. Actin polymerization was determined by confocal microscopy. Stress-activated channel activity was measured by patch clamp. Myogenic tone developing in response to pressure was dramatically decreased by SRF deletion (5.9+/-2.3%) compared with control (16.3+/-3.2%). This defect was accompanied by decreases in actin polymerization, filamin A, myosin light chain kinase and myosin light chain expression level, and stress-activated channel activity and sensitivity in response to pressure. Contractions induced by phenylephrine or U46619 were not modified, despite a higher sensitivity to p38 blockade; this highlights a compensatory pathway, allowing normal receptor-dependent contraction. CONCLUSIONS: This study shows for the first time that SRF has a major part to play in the control of local blood flow via its central role in pressure-induced myogenic tone in resistance arteries

Selective CO₂ capture in metal-organic frameworks with azine-functionalized pores generated by mechanosynthesis

Two new three-dimensional porous Zn(II)-based metal-organic frameworks, containing azine-functionalized pores, have been readily and quickly isolated via mechanosynthesis, by using a nonlinear dicarboxylate and linear N-donor ligands. The use of nonfunctionalized and methyl-functionalized N-donor ligands has led to the formation of frameworks with different topologies and metal-ligand connectivities and therefore different pore sizes and accessible volumes. Despite this, both metal-organic frameworks (MOFs) possess comparable BET surface areas and CO₂ uptakes at 273 and 298 K at 1 bar. The network with narrow and interconnected pores in three dimensions shows greater affinity for CO compared to the network with one-dimensional and relatively large pores-attributable to the more effective interactions with the azine groups

178Hg and asymmetric fission of neutron-deficient pre-actinides

International audienceFission at low excitation energy is an ideal playground to probe the impact of nuclear structure on nuclear dynamics. While the importance of structural effects in the nascent fragments is well established in the (trans-)actinide region, the observation of asymmetric fission in several neutron-deficient pre-actinides can be explained by various mechanisms. To deepen our insight into that puzzle, an innovative approach based on inverse kinematics and an enhanced version of the VAMOS++ heavy-ion spectrometer was implemented at the GANIL facility, Caen. Fission of Hg178 was induced by fusion of Xe124 and Fe54. The two fragments were detected in coincidence using VAMOS++ supplemented with a new SEcond Detection arm. For the first time in the pre-actinide region, access to the pre-neutron mass and total kinetic energy distributions, and the simultaneous isotopic identification of one the fission fragment, was achieved. The present work describes the experimental approach, and discusses the pre-neutron observables in the context of an extended asymmetric-fission island located southwest of Pb208. A comparison with different models is performed, demonstrating the importance of this new asymmetric-fission island for elaborating on driving effects in fission

Effectiveness and cost-effectiveness of transmural collaborative care with consultation letter (TCCCL) and duloxetine for major depressive disorder (MDD) and (sub)chronic pain in collaboration with primary care: design of a randomized placebo-controlled multi-Centre trial: TCC:PAINDIP

__Abstract__ Background: The comorbidity of pain and depression is associated with high disease burden for patients in terms of disability, wellbeing, and use of medical care. Patients with major and minor depression often present themselves with pain to a general practitioner and recognition of depression in such cases is low, but evolving. Also, physical symptoms, including pain, in major depressive disorder, predict a poorer response to treatment. A multi-faceted, patient-tailored treatment programme, like collaborative care, is promising. However, treatment of chronic pain conditions in depressive patients has, so far, received limited attention in research. Cost effectiveness of an integrated approach of pain in depressed patients has not been studied. This article describes the aims and design of a study to evaluate effects and costs of collaborative care with the antidepressant duloxetine for patients with pain symptoms and a depressive disorder, compared to collaborative care with placebo and compared to duloxetine alone

The Rodin-Ohno hypothesis that two enzyme superfamilies descended from one ancestral gene: an unlikely scenario for the origins of translation that will not be dismissed

Background Because amino acid activation is rate-limiting for uncatalyzed protein synthesis, it is a key puzzle in understanding the origin of the genetic code. Two unrelated classes (I and II) of contemporary aminoacyl-tRNA synthetases (aaRS) now translate the code. Observing that codons for the most highly conserved, Class I catalytic peptides, when read in the reverse direction, are very nearly anticodons for Class II defining catalytic peptides, Rodin and Ohno proposed that the two superfamilies descended from opposite strands of the same ancestral gene. This unusual hypothesis languished for a decade, perhaps because it appeared to be unfalsifiable. Results The proposed sense/antisense alignment makes important predictions. Fragments that align in antiparallel orientations, and contain the respective active sites, should catalyze the same two reactions catalyzed by contemporary synthetases. Recent experiments confirmed that prediction. Invariant cores from both classes, called Urzymes after Ur = primitive, authentic, plus enzyme and representing ~20% of the contemporary structures, can be expressed and exhibit high, proportionate rate accelerations for both amino-acid activation and tRNA acylation. A major fraction (60%) of the catalytic rate acceleration by contemporary synthetases resides in segments that align sense/antisense. Bioinformatic evidence for sense/antisense ancestry extends to codons specifying the invariant secondary and tertiary structures outside the active sites of the two synthetase classes. Peptides from a designed, 46-residue gene constrained by Rosetta to encode Class I and II ATP binding sites with fully complementary sequences both accelerate amino acid activation by ATP ~400 fold. Conclusions Biochemical and bioinformatic results substantially enhance the posterior probability that ancestors of the two synthetase classes arose from opposite strands of the same ancestral gene. The remarkable acceleration by short peptides of the rate-limiting step in uncatalyzed protein synthesis, together with the synergy of synthetase Urzymes and their cognate tRNAs, introduce a new paradigm for the origin of protein catalysts, emphasize the potential relevance of an operational RNA code embedded in the tRNA acceptor stems, and challenge the RNA-World hypothesis. Reviewers This article was reviewed by Dr. Paul Schimmel (nominated by Laura Landweber), Dr. Eugene Koonin and Professor David Ardell

Emissions de particules issues d’un moteur essence à injection directe : Impact du catalyseur trois voies

National @ AIR+ABO:BRM:NCA:LRE:BDA:PVEInternational audienceNon

Ultrafine particulate matter emissions from a gasoline direct injection engine

International @ AIR+BRM:ABO:MTS:NCA:LRE:BDA:PVEInternational audienceEpidemiological studies have linked exposure to particles matter less than 2.5 microns in diameter (PM2.5) with adverse health (cardiovascular or pulmonary diseases that would cause premature death). The contribution of the transport sector to the total concentration of PM2.5 in the ambient air is 12% [1]. This value represents an average which likely is higher in areas near emission sources (i.e. urban area). PM abatement in exhausts of gasoline direct injection (GDI) engines, which aims to improve fuel efficiency, will be necessary due to the strengthening of the European legislations. GDI engines offer a number of opportunities for improving fuel efficiency, such as reducing pumping losses, charge air cooling, and downsizing when turbocharged [2]. However, direct injection of fuel into the engine cylinder is susceptible to incomplete fuel evaporation and to fuel impingement on piston and cylinder walls, both of which lead to combusti on of liquid fuel and, consequently, to PM emissions increase [3]. Gasoline Particulate Filters (GPF) are currently developed to mechanically filter the soot particles emitted by GDI engines. The particle sizes in this case are typically smaller in comparison with diesel engines [4]. Ultrafine particulate (UFP) matter (1-40 nm) emissions from a GDI engine (1.6 L) were characterized as a function of the engine operating regime in terms of particle numbers and size distributions. Exhaust gas samples were analyzed upstream and downstream a three-way converter (TWC), as well as downstream a GPF, i.e. at the exhaust outlet. UFPs were analyzed with a Scanning Mobility Particle Sizer equipped with a dielectric barrier discharge, a differential mobility analyzer (176 channels) to classify the PM size range that enters into a Faraday-Cup Electrometer (FCE) to count the charged particulates (SMPS+E, Grimm). After a two stage dilution (realized by FPS4000, DEKATI), the sampled aerosol was analyzed in the range 1 to 38 nm. SMPS+E data were compared with those of a SMPS (TSI, model 3080, PM size range 3-150 nm) and a DMS (Differential Mobility Spectrometer, Cambustion, PM size range analysis 5-1000 nm). In addition, the fraction of the elemental carbon in PM was estim ated with a Multi-Angle Absorption Photometer (MAAP, Thermo Scientific, model 5012). UFPs with diameters lower than 20 nm was detected upstream the TWC. UFPs total concentrations were high, in the range 2 20 1014 part/m3 depending on the engine load. UFPs size distributions were found to be bimodal with mean diameters around 2-3 nm and 10 nm, respectively. The impact of TWC on UFP concentration and size was significant since a large part of UFPs, lower than 10 nm, was removed. Furthermore, the overall UFPs number was divided by one order of magnitude. The filtering efficiency for UFPs of the GPF was found to be high since no UFPs was detectable using the SMPS+E downstream the GPF (Fig. 1). These results will be discussed in relation with PM analysis in the range 5 200 nm, carbon elemental concentration as well as gas pollutant emissions. Figure 1: UFPs size distributions at 2500 rpm/ 13 bar. Dilution ratio= 6. Acknowledgements The authors would like to thank the Agence National de la Recherche (ANR) for the financial support of the TRIPTIC-H project (N°ANR-11-VPTT-003-05). References [1] WHO, 2006a: Health risks of particulate matter from long-range transboundary air pollution. WHO report E88189, WHO Regional Office for Europe, Copenhagen, Denmark. [2] J. Yi, S. Wooldridge, G. Coulson, J. Hilditch, C.O. Lyer, P. Moilanen, G. Papaioannou, D. Reich, M. Shelby, B. VanDer-Wege, C. Weaver, Z. Xu, G. Davis, B. Hinds, A. Schamel, SAE Technical Paper. 2009-01-1494 (2009). [3] S. J. Harris, M. M. Maricq, Aerosol Science 32 (2001) 749. [4] M.M. Maricq, Combustion and Flame. 159 (2012) 170

Ultrafine particulate matter emissions from a gasoline direct injection engine

International @ AIR+BRM:ABO:MTS:NCA:LRE:BDA:PVEInternational audienceEpidemiological studies have linked exposure to particles matter less than 2.5 microns in diameter (PM2.5) with adverse health (cardiovascular or pulmonary diseases that would cause premature death). The contribution of the transport sector to the total concentration of PM2.5 in the ambient air is 12% [1]. This value represents an average which likely is higher in areas near emission sources (i.e. urban area). PM abatement in exhausts of gasoline direct injection (GDI) engines, which aims to improve fuel efficiency, will be necessary due to the strengthening of the European legislations. GDI engines offer a number of opportunities for improving fuel efficiency, such as reducing pumping losses, charge air cooling, and downsizing when turbocharged [2]. However, direct injection of fuel into the engine cylinder is susceptible to incomplete fuel evaporation and to fuel impingement on piston and cylinder walls, both of which lead to combusti on of liquid fuel and, consequently, to PM emissions increase [3]. Gasoline Particulate Filters (GPF) are currently developed to mechanically filter the soot particles emitted by GDI engines. The particle sizes in this case are typically smaller in comparison with diesel engines [4]. Ultrafine particulate (UFP) matter (1-40 nm) emissions from a GDI engine (1.6 L) were characterized as a function of the engine operating regime in terms of particle numbers and size distributions. Exhaust gas samples were analyzed upstream and downstream a three-way converter (TWC), as well as downstream a GPF, i.e. at the exhaust outlet. UFPs were analyzed with a Scanning Mobility Particle Sizer equipped with a dielectric barrier discharge, a differential mobility analyzer (176 channels) to classify the PM size range that enters into a Faraday-Cup Electrometer (FCE) to count the charged particulates (SMPS+E, Grimm). After a two stage dilution (realized by FPS4000, DEKATI), the sampled aerosol was analyzed in the range 1 to 38 nm. SMPS+E data were compared with those of a SMPS (TSI, model 3080, PM size range 3-150 nm) and a DMS (Differential Mobility Spectrometer, Cambustion, PM size range analysis 5-1000 nm). In addition, the fraction of the elemental carbon in PM was estim ated with a Multi-Angle Absorption Photometer (MAAP, Thermo Scientific, model 5012). UFPs with diameters lower than 20 nm was detected upstream the TWC. UFPs total concentrations were high, in the range 2 20 1014 part/m3 depending on the engine load. UFPs size distributions were found to be bimodal with mean diameters around 2-3 nm and 10 nm, respectively. The impact of TWC on UFP concentration and size was significant since a large part of UFPs, lower than 10 nm, was removed. Furthermore, the overall UFPs number was divided by one order of magnitude. The filtering efficiency for UFPs of the GPF was found to be high since no UFPs was detectable using the SMPS+E downstream the GPF (Fig. 1). These results will be discussed in relation with PM analysis in the range 5 200 nm, carbon elemental concentration as well as gas pollutant emissions. Figure 1: UFPs size distributions at 2500 rpm/ 13 bar. Dilution ratio= 6. Acknowledgements The authors would like to thank the Agence National de la Recherche (ANR) for the financial support of the TRIPTIC-H project (N°ANR-11-VPTT-003-05). References [1] WHO, 2006a: Health risks of particulate matter from long-range transboundary air pollution. WHO report E88189, WHO Regional Office for Europe, Copenhagen, Denmark. [2] J. Yi, S. Wooldridge, G. Coulson, J. Hilditch, C.O. Lyer, P. Moilanen, G. Papaioannou, D. Reich, M. Shelby, B. VanDer-Wege, C. Weaver, Z. Xu, G. Davis, B. Hinds, A. Schamel, SAE Technical Paper. 2009-01-1494 (2009). [3] S. J. Harris, M. M. Maricq, Aerosol Science 32 (2001) 749. [4] M.M. Maricq, Combustion and Flame. 159 (2012) 170