New meanings from old buildings

The three modest house projects described here are by three fellow travellers — the two authors and David Lea — interested in the Organic side of Modernism. Conversational partners who have worked together in various capacities over many years, they share a common conviction about ‘working with the given

Aprotinin reduces cardiac troponin I release and inhibits apoptosis of polymorphonuclear cells during off-pump coronary artery bypass surgery

Objectives: In addition to blood-sparing effects, aprotinin may have cardioprotective and anti-inflammatory effects during cardiopulmonary bypass-assisted cardiac surgery. In this study, the authors examined whether aprotinin had cardioprotective and/or anti-inflammatory effects in patients undergoing off-pump coronary artery bypass grafting. Design: A prospective randomized clinical trial. Setting: University hospital. Participants: Fifty patients were randomized to control (n = 25) or aprotinin treatment (n = 25) groups. Interventions: Aprotinin was given as a loading dose (2 x 10(6) KIU) followed by a continuous infusion at 5 x 10(5) KIU/h until skin closure. Measurements and Main Results: Blood samples for cardiac troponin I; interleukin-6, interleukin-8, and interleukin-10; tumor necrosis factor a; and elastase were taken after anesthesia induction, completion of revascularization, and 6 hours, 12 hours, and 24 hours after revascularization. Blood samples were taken to assess for apoptosis in polymorphonuclear cells. Baseline plasma levels for cardiac troponin I did not differ between groups but were significantly lower in aprotinin-treated patients at the time of revascularization (P = 0.03) and 6 hours (p = 0.004) and 24 hours (p = 0.03) later. Aprotinin significantly reduced apoptosis in polymorphonuclear cells compared with control-treated patients (p = 0.04). There were no differences in plasma cytokine or elastase levels between groups. Conclusions: The authors conclude that aprotinin reduces perioperative cardiac troponin I release and attenuates apoptosis in polymorphonuclear cells but has no significant effects on plasma cytokine levels in patients undergoing off-pump coronary artery bypass graft surgery

Auger mediated quantum sticking of positrons to surfaces: Evidence for single step transition from a scattering state to a surface image potential bound state

We present the observation of an efficient mechanism for positron sticking to surfaces termed here Auger mediated quantum sticking. In this process the energy associated with the positrons transition from an unbound scattering state to a bound image potential state is coupled to a valence electron which can then have sufficient energy to leave the surface. Compelling evidence for this mechanism is found in a narrow secondary electron peak observed at incident positron kinetic energies well below the electron work function.Comment: 4 pages, 4 figure

Ca 2+ signalling in urethral interstitial cells of Cajal

Interstitial cells of Cajal (ICC) in the urethra have been proposed as specialized pacemakers that are involved in the generation of urethral tone and therefore the maintenance of urinary continence. Recent studies on freshly dispersed ICC from the urethra of rabbits have demonstrated that pacemaker activity in urethra ICC is characterized by spontaneous transient depolarizations (STDs) under current clamp and spontaneous transient inward currents (STICs) under voltage clamp. When these events were simultaneously recorded with changes in intracellular Ca 2+ (using a Nipkow spinning disk confocal microscope) they were found to be associated with global Ca 2+ oscillations. In this short review we will consider some of these recent findings regarding the contribution of intracellular Ca 2+ stores and Ca 2+ influx to the generation of pacemaker activity in urethral ICC with particular emphasis on the contribution of reverse Na + /Ca 2+ exchange (NCX)

Contribution of K v 2.1 channels to the delayed rectifier current in freshly dispersed smooth muscle cells from rabbit urethra

We have characterized the native voltage-dependent K + (K v ) current in rabbit urethral smooth muscle cells (RUSMC) and compared its pharmacological and biophysical properties with K v 2.1 and K v 2.2 channels cloned from the rabbit urethra and stably expressed in HEK 293 cells (HEK Kv2.1 and HEK Kv2.2 ). RUSMC were perfused with Hanks' solution at 37°C and studied using the patch clamp technique with K + -rich pipette solutions. Cells were bathed in 100 nM penitrem A (Pen A) to block large conductance Ca 2+ -activated K + (BK) currents and depolarized to +40 mV for 500 ms to evoke K v currents. These were unaffected by margatoxin, κ-dendrotoxin or α-dendrotoxin (100 nM, n=3-5), but were blocked by stromatoxin-1 (ScTx, IC 50 ~130 nM), consistent with the idea that the currents were carried through K v 2 channels. RNA was detected for K v 2.1 K v 2.2 and the silent subunit K v 9.3 in urethral smooth muscle. Immunocytochemistry showed membrane staining for both K v 2 subtypes and K v 9.3 in isolated RUSMC. HEK Kv2.1 and HEK Kv2.2 currents were blocked in a concentration dependent manner by ScTx with estimated IC 50 values of ~150 nM (K v 2.1, n=5) and 70 nM (K v 2.2, n=6). The mean V 1/2 of inactivation of the USMC K v current was – 56±3 mV (n=9). This was similar to the HEK Kv2.1 current (–55 ± 3 mV, n=13) but significantly different from the HEK Kv2.2 currents (-30 ± 3 mV, n=11). Action potentials (AP) evoked from RUSMC studied under current clamp mode were unaffected by ScTx. However when ScTx was applied in the presence of Pen A, the AP duration was significantly prolonged. Similarly, ScTx increased the amplitude of spontaneous contractions threefold, but only after Pen A application. These data suggest that K v 2.1 channels contribute significantly to the K v current in RUSMC

Experimental investigation of aminoacetonitrile formation through the Strecker synthesis in astrophysical-like conditions: reactivity of methanimine (CH2NH), ammonia (NH3), and hydrogen cyanide (HCN)

International audienceAstronomy & Astrophysics Experimental investigation of aminoacetonitrile formation through the Strecker synthesis in astrophysical-like conditions: reactivity of methanimine (CH 2 NH), ammonia (NH 3), and hydrogen cyanide (HCN) ABSTRACT Context. Studing chemical reactivity in astrophysical environments is an important means for improving our understanding of the origin of the organic matter in molecular clouds, in protoplanetary disks, and possibly, as a final destination, in our solar system. Laboratory simulations of the reactivity of ice analogs provide important insight into the reactivity in these environments. Here, we use these experimental simulations to investigate the Strecker synthesis leading to the formation of aminoacetonitrile in astrophysical-like conditions. The aminoacetonitrile is an interesting compound because it was detected in SgrB2, hence could be a precursor of the smallest amino acid molecule, glycine, in astrophysical environments. Aims. We present the first experimental investigation of the formation of aminoacetonitrile NH 2 CH 2 CN from the thermal processing of ices including methanimine (CH 2 NH), ammonia (NH 3), and hydrogen cyanide (HCN) in interstellar-like conditions without VUV photons or particules. Methods. We use Fourier Transform InfraRed (FTIR) spectroscopy to monitor the ice evolution during its warming. Infrared spec-troscopy and mass spectroscopy are then used to identify the aminoacetonitrile formation. Results. We demonstrate that methanimine can react with − CN during the warming of ice analogs containing at 20 K methanimine, ammonia, and [NH + 4 − CN] salt. During the ice warming, this reaction leads to the formation of poly(methylene-imine) polymers. The polymer length depend on the initial ratio of mass contained in methanimine to that in the [NH + 4 − CN] salt. In a methanimine excess, long polymers are formed. As the methanimine is progressively diluted in the [NH + 4 − CN] salt, the polymer length decreases until the aminoacetonitrile formation at 135 K. Therefore, these results demonstrate that aminoacetonitrile can be formed through the second step of the Strecker synthesis in astrophysical-like conditions

GrapeTree : visualization of core genomic relationships among 100,000 bacterial pathogens

Current methods struggle to reconstruct and visualise the genomic relationships of ≥100,000 bacterial genomes. GrapeTree facilitates the analyses of allelic profiles from 10,000's of core genomes within a web browser window. GrapeTree implements a novel minimum spanning tree algorithm to reconstruct genetic relationships despite missing data together with a static "GrapeTree Layout" algorithm to render interactive visualisations of large trees. GrapeTree is a stand-along package for investigating Newick trees plus associated metadata and is also integrated into EnteroBase to facilitate cutting edge navigation of genomic relationships among >160,000 genomes from bacterial pathogens. The GrapeTree package was released under the GPL v3.0 Licence

GrapeTree : visualization of core genomic relationships among 100,000 bacterial pathogens

Current methods struggle to reconstruct and visualise the genomic relationships of ≥100,000 bacterial genomes. GrapeTree facilitates the analyses of allelic profiles from 10,000's of core genomes within a web browser window. GrapeTree implements a novel minimum spanning tree algorithm to reconstruct genetic relationships despite missing data together with a static "GrapeTree Layout" algorithm to render interactive visualisations of large trees. GrapeTree is a stand-along package for investigating Newick trees plus associated metadata and is also integrated into EnteroBase to facilitate cutting edge navigation of genomic relationships among >160,000 genomes from bacterial pathogens. The GrapeTree package was released under the GPL v3.0 Licence

Impact of botanical oils on polyunsaturated fatty acid metabolism and leukotriene generation in mild asthmatics

Background: Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as γ linolenic acid (GLA, 18:3n-6), stearidonic acid (SDA, 18:4n-3) and α linolenic acid (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic acid (AA) metabolism and improve inflammatory disorders. Methods: The diet of mild asthmatics patients was supplemented for three weeks with varying doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week wash out period followed. The impact of these dietary manipulations was evaluated for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo leukotriene generation from stimulated leukocytes. Results: Supplementation with several EO/BO combinations increased circulating 20–22 carbon (20–22C) PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo-gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and inflammation without impacting circulating AA levels. BO/EO combinations also inhibited ex vivo leukotriene generation with some combinations attenuating cysteinyl leukotriene generation in stimulated basophils by >50% and in stimulated neutrophils by >35%. Conclusions: This study shows that dietary supplementation with BO/EO alters 20–22C PUFA levels and attenuates leukotriene production in a manner consistent with a reduction in inflammation

LTC4 synthase polymorphism modifies efficacy of botanical seed oil combination in asthma

Botanical seed oils reduce the generation of leukotrienes in patients with asthma. Our objective was to determine the efficacy of a botanical seed oil combination against airflow obstruction in asthma, and to determine the pharmacogenomic effect of the leukotriene C4 synthase (LTC4S) polymorphism A-444C. We conducted a randomized, double-blind, placebo-controlled, cross-over clinical trial in mild to moderate asthmatics to determine the change in FEV1 after 6 weeks of therapy with borage and echium seed oils versus corn oil placebo. We also examined the effect of the variant LTC4S -444C allele on the change in lung function. We did not identify a difference in FEV1 in the study cohort as a whole (n = 28), nor in the group of A homozygotes. In the C allele carriers (n = 9), FEV1 improved by 3% after treatment with borage and echium seed oils and declined by 4% after placebo corn oil (p = 0.02). All 9 C allele carriers demonstrated an improvement in their FEV1 on active treatment compared to placebo as compared to only 7 out of 19 A allele homozygotes (p = 0.007). We observed transient differences in ex vivo leukotriene generation from circulating basophils and granulocytes. We did not observe significant differences in urinary LTE4 levels. We conclude that compared to corn oil, a combination of borage and echium seed oils improves airflow obstruction in mild to moderate asthmatics who carry the variant allele in the LTC4S gene (A-444C). Botanical oil supplementation may have therapeutic potential in asthma if used in a personalized manner. Trial registration: This trial was registered at http://www.clinicaltrials.gov as NCT00806442