54 research outputs found
Proton translocation by cytochrome c oxidase reconstituted into proteoliposomes
Cytochrome c oxidase .inserted into proteoliposomes
translocates protons with a stoichiometry of approx-,
imately 0.4-0.6 H+/e- in the presence of valinomycin
plus pottasium. The existance .ofsuchproton translocation
is .supportedby experiments with lauryl maltoside
which abolished the pulses but~~d not inhibit cyt.
c binding .or oxidase turnover. Pulses with K3FeCN6 did
not induce acidification further supporting vectorial
proton transport by cyt ..aa3 . Upon lowering the ionic
strength and pulsing with ferrocytochrome c, H+/eratios
increased. This increase is attributed to scaler
proton release consequent upon cyt.c-phospholipid binding.
Oxygen pulses at low ionic strength however did not exhibit
this large scaler increase in H+/e- ratios.A-small increase
was observed upon .02 pul'sing at·low ionic strengt.h. This
increase was KeN and, ,pcep sensitive and thus possibly due
to a redox linked scaler deprotonation. Increases in the
H+/e- ratio also occurred ifp~lses ,were performed in the
presence of nonactin rather.than valinomycin.
The fluorescent pH indicator pyranine was internally
trapped inaa3 conta~ning "proteoliposomes. Internal alkalinization,
as mon,itored by pyranine fluorescence leads
to a of approx.imately 0.35 units, which is proportional
to electron flux. This internal alkalinization was also
DCCD sensitive, being inhibited by approximately 50%. This
50% inhibition of internal alkalinization supports the existance of vectorial proton transport
Type 1 plasminogen activator inhibitor binds to fibrin via vitronectin
Type 1 plasminogen activator inhibitor (PAI-1), the primary inhibitor of tissue-type plasminogen activator (t-PA), circulates as a complex with the abundant plasma glycoprotein, vitronectin. This interaction stabilizes the inhibitor in its active conformation. In this report, the effects of vitronectin on the interactions of PAI-1 with fibrin clots were studied. Confocal microscopic imaging of platelet-poor plasma clots reveals that essentially all fibrin-associated PAI-1 colocalizes with fibrin-bound vitronectin. Moreover, formation of platelet-poor plasma clots in the presence of polyclonal antibodies specific for vitronectin attenuated the inhibitory effects of PAI-1 on t-PA-mediated fibrinolysis. Addition of vitronectin during clot formation markedly potentiates PAI-1-mediated inhibition of lysis of 125I-labeled fibrin clots by t-PA. This effect is dependent on direct binding interactions of vitronectin with fibrin. There is no significant effect of fibrin-associated vitronectin on fibrinolysis in the absence of PAI-1. The binding of PAI-1 to fibrin clots formed in the absence of vitronectin was characterized by a low affinity (Kd ~ 3.5 μM) and rapid loss of PAI-1 inhibitory activity over time. In contrast, a high affinity and stabilization of PAI-1 activity characterized the cooperative binding of PAI- 1 to fibrin formed in the presence of vitronectin. These findings indicate that plasma PAI-1-vitronectin complexes can be localized to the surface of fibrin clots; by this localization, they may modulate fibrinolysis and clot reorganization
Scientific Objectives of Einstein Telescope
The advanced interferometer network will herald a new era in observational
astronomy. There is a very strong science case to go beyond the advanced
detector network and build detectors that operate in a frequency range from 1
Hz-10 kHz, with sensitivity a factor ten better in amplitude. Such detectors
will be able to probe a range of topics in nuclear physics, astronomy,
cosmology and fundamental physics, providing insights into many unsolved
problems in these areas.Comment: 18 pages, 4 figures, Plenary talk given at Amaldi Meeting, July 201
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
Constraints on cosmic strings using data from the first Advanced LIGO observing run
Cosmic strings are topological defects which can be formed in grand unified theory scale phase transitions in the early universe. They are also predicted to form in the context of string theory. The main mechanism for a network of Nambu-Goto cosmic strings to lose energy is through the production of loops and the subsequent emission of gravitational waves, thus offering an experimental signature for the existence of cosmic strings. Here we report on the analysis conducted to specifically search for gravitational-wave bursts from cosmic string loops in the data of Advanced LIGO 2015-2016 observing run (O1). No evidence of such signals was found in the data, and as a result we set upper limits on the cosmic string parameters for three recent loop distribution models. In this paper, we initially derive constraints on the string tension Gμ and the intercommutation probability, using not only the burst analysis performed on the O1 data set but also results from the previously published LIGO stochastic O1 analysis, pulsar timing arrays, cosmic microwave background and big-bang nucleosynthesis experiments. We show that these data sets are complementary in that they probe gravitational waves produced by cosmic string loops during very different epochs. Finally, we show that the data sets exclude large parts of the parameter space of the three loop distribution models we consider
WSES guidelines for management of Clostridium difficile infection in surgical patients
In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe
WSES guidelines for management of Clostridium difficile infection in surgical patients
Analysis of biobanked serum from a mycobacterium avium subsp paratuberculosis bovine infection model confirms the remarkable stability of circulating mirna profiles and defines a bovine serum mirna repertoire
Johne's Disease (JD) is a chronic enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Current disease control strategies are hampered by the lack of sensitive and specific diagnostic modalities. Therefore, novel diagnostic and prognostic tools are needed, and circulating microRNAs (miRNAs) may hold potential in this area. The aims of this study were twofold: (i) to address the stability of miRNA in bovine sera from biobanked samples, and (ii) to assess the potential of miRNAs as biomarkers for JD disease progression. To address these aims we used bovine sera from an experimental MAP infection model that had been stored at -20°C for over a decade, allowing us to also assess the stability of miRNA profiles in biobanked serum samples through comparison with fresh sera. Approximately 100â€"200 intact miRNAs were identified in each sample with 83 of these being consistently detected across all 57 samples. The miRNA profile of the biobanked sera stored at -20°C for over 10 years was highly similar to the profile o
Canonical and dominant isomiR differences.
<p>A) bta-miR-22-3p total abundance profile over time (left) and for 2 isomiRs (right), both are shorter 3’ variants. Analysing these isomiRs individually allows them to be detected as being differentially expressed over time. B) bta-miR-22-3p isomiR relative abundances. The canonical form, labelled <i>exact</i>, is only fourth most abundant. C) The canonical and dominant isomiRs differ in >50% of cases. Shown in the plot are the corresponding percentages between the 2 isoforms, when different. (By definition <i>dominant</i> means highest percentage of reads). For points in the top left of the plots, the actual canonical form is insignificant. Note the lower number of points for the 10–15 year (CVI) dataset.</p
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