195 research outputs found
Ion-induced transient potential fluctuations facilitate pore formation and cation transport through lipid membranes
Unassisted ion transport through lipid membranes plays a crucial role in many
cell functions without which life would not be possible, yet the precise
mechanism behind the process remains unknown due to its molecular complexity.
Here, we demonstrate a direct link between membrane potential fluctuations and
divalent ion transport. High-throughput wide-field second harmonic (SH)
microscopy shows that membrane potential fluctuations are universally found in
lipid bilayer systems. Molecular dynamics simulations reveal that such
variations in membrane potential reduce the free energy cost of transient pore
formation and increase the ion flux across an open pore. These transient pores
can act as conduits for ion transport, which we SH image for a series of
divalent cations (Cu, Ca, Ba, Mg) passing through
GUV membranes. Combining the experimental and computational results, we show
that permeation through pores formed via an ion-induced electrostatic field is
a viable mechanism for unassisted ion transport.Comment: 8 pages, 2 figure
Imaging the Heterogeneity of the Oxygen Evolution Reaction on Gold Electrodes Operando: Activity is Highly Local
Understanding the mechanism of the oxygen evolution reaction (OER), the oxidative half of electrolytic water splitting, has proven challenging. Perhaps the largest hurdle has been gaining experimental insight into the active site of the electrocatalyst used to facilitate this chemistry. Decades of study have clarified that a range of transition-metal oxides have particularly high catalytic activity for the OER. Unfortunately, for virtually all of these materials, metal oxidation and the OER occur at similar potentials. As a result, catalyst surface topography and electronic structure are expected to continuously evolve under reactive conditions. Gaining experimental insight into the OER mechanism on such materials thus requires a tool that allows spatially resolved characterization of the OER activity. In this study, we overcome this formidable experimental challenge using second harmonic microscopy and electrochemical methods to characterize the spatial heterogeneity of OER activity on polycrystalline Au working electrodes. At moderately anodic potentials, we find that the OER activity of the electrode is dominated by <1% of the surface area and that there are two types of active sites. The first is observed at potentials positive of the OER onset and is stable under potential cycling (and thus presumably extends multiple layers into the bulk gold electrode). The second occurs at potentials negative of the OER onset and is removed by potential cycling (suggesting that it involves a structural motif only 1–2 Au layers deep). This type of active site is most easily understood as the catalytically active species (hydrous oxide) in the so-called incipient hydrous oxide/adatom mediator model of electrocatalysis. Combining the ability we demonstrate here to characterize the spatial heterogeneity of OER activity with a systematic program of electrode surface structural modification offers the possibility of creating a generation of OER electrocatalysts with unusually high activity
Ultrasensitive Label-Free Detection of Protein-Membrane Interaction Exemplified by Toxin-Liposome Insertion.
Measuring the high-affinity binding of proteins to liposome membranes remains a challenge. Here, we show an ultrasensitive and direct detection of protein binding to liposome membranes using high throughput second harmonic scattering (SHS). Perfringolysin O (PFO), a pore-forming toxin, with a highly membrane selective insertion into cholesterol-rich membranes is used. PFO inserts only into liposomes with a cholesterol concentration >30%. Twenty mole-percent cholesterol results in neither SHS-signal deviation nor pore formation as seen by cryo-electron microscopy of PFO and liposomes. PFO inserts into cholesterol-rich membranes of large unilamellar vesicles in an aqueous solution with Kd = (1.5 ± 0.2) × 10-12 M. Our results demonstrate a promising approach to probe protein-membrane interactions below sub-picomolar concentrations in a label-free and noninvasive manner on 3D systems. More importantly, the volume of protein sample is ultrasmall (<10 μL). These findings enable the detection of low-abundance proteins and their interaction with membranes
Visible-Light-Driven Rotation of Molecular Motors in a Dual-Function Metal-Organic Framework Enabled by Energy Transfer
The visible-light-driven rotation of an overcrowded alkene-based molecular motor strut in a dual-function metal-organic framework (MOF) is reported. Two types of functional linkers, a palladium-porphyrin photosensitizer and a bispyridine-derived molecular motor, were used to construct the framework capable of harvesting low-energy green light to power the rotary motion. The molecular motor was introduced in the framework using the postsynthetic solvent-assisted linker exchange (SALE) method, and the structure of the material was confirmed by powder (PXRD) and single-crystal X-ray (SC-XRD) diffraction. The large decrease in the phosphorescence lifetime and intensity of the porphyrin in the MOFs upon introduction of the molecular motor pillars confirms efficient triplet-to-triplet energy transfer between the porphyrin linkers and the molecular motor. Near-infrared Raman spectroscopy revealed that the visible light-driven rotation of the molecular motor proceeds in the solid state at rates similar to those observed in solution
Ethanol Pharmacokinetics in Neonates Secondary to Medication Administration
Purpose:
Ethanol serves as a solvent and microbial preservative in oral liquid medications and is the second most commonly used solvent in liquid medications following water. Despite widespread use of ethanol in liquid medications for neonates, the pharmacokinetics and toxicity of ethanol in young children are not well described. The aim of the current study is to quantify blood ethanol levels in neonates secondary to oral ethanol containing medications.
Methods:
Neonates who received either oral phenobarbital (15% ethanol) and/or oral dexamethasone (30% ethanol) per standard of care were eligible for enrollment. A maximum of 6 blood samples per patient (4.5 mL total) were taken over the study period. Blood samples were collected via heel stick at the time of clinical laboratory collections or following a specific collection for study purposes. In addition, blood samples were collected from neonates receiving sublingual buprenorphine (30% ethanol) for neonatal abstinence syndrome from a separate clinical study. Blood ethanol levels were measured using a validated headspace gas chromatography-mass spectrometry method utilizing micro-volume ( ̴100uL) plasma samples. The limit of detection and lower limit of quantification for the assay were 0.1 mg/L and 0.5 mg/L respectively.
Results:
A total of 39 plasma samples from 15 neonates who were on ethanol containing medications were collected over the study period. Four neonates were exposed to phenobarbital and/or dexamethasone, while eleven neonates were exposed to buprenorphine alone or in combination with phenobarbital. Patients were exposed to an average of 71.6 mg/kg (range 13.1 to 215 mg/kg) of ethanol after a single dose of an ethanol containing medication. Blood ethanol levels were detectable in 98% (38/39) of samples, quantifiable in 67% (26/39) of samples, and ranged from below detection to 85.4 mg/L. Ethanol was rapidly cleared and did not accumulate with current dosing regimens.
Conclusion:
Ethanol intake secondary to medication administration varied widely. Blood ethanol levels in neonates were low and ethanol was eliminated rapidly after a single dose of oral medications that contained a sizable fraction of ethanol.https://jdc.jefferson.edu/petposters/1000/thumbnail.jp
The C-Band All-Sky Survey (C-BASS): New Constraints on the Integrated Radio Spectrum of M 31
The Andromeda galaxy (M31) is our closest neighbouring spiral galaxy, making
it an ideal target for studying the physics of the interstellar medium in a
galaxy very similar to our own. Using new observations of M31 at 4.76GHz by the
C-Band All-Sky Survey (C-BASS), and all available radio data at
resolution, we produce the integrated spectrum and put new constraints on the
synchrotron spectral index and anomalous microwave emission (AME) from M31. We
use aperture photometry and spectral modelling to fit for the integrated
spectrum of M31, and subtract a comprehensive model of nearby background radio
sources. The AME in M31 is detected at significance with a peak near
30GHz and flux density Jy. The synchrotron spectral index of M31
is flatter than our own Galaxy at with no strong
evidence of spectral curvature. The emissivity of AME, averaged over the total
emission from M31 is lower than typical AME sources in our Galaxy, implying
that AME is not uniformly distributed throughout M31 and instead is likely
confined to sub-regions -- this will need to be confirmed using future higher
resolution observations around 20--30GHz.Comment: 16 pages, 6 figures, submitted to MNRA
COMAP Early Science: VI. A First Look at the COMAP Galactic Plane Survey
We present early results from the COMAP Galactic Plane Survey conducted
between June 2019 and April 2021, spanning in Galactic
longitude and |b|<1.\!\!^{\circ}5 in Galactic latitude with an angular
resolution of . The full survey will span -
and will be the first large-scale radio continuum survey at
GHz with sub-degree resolution. We present initial results from the first part
of the survey, including diffuse emission and spectral energy distributions
(SEDs) of HII regions and supernova remnants. Using low and high frequency
surveys to constrain free-free and thermal dust emission contributions, we find
evidence of excess flux density at GHz in six regions that we interpret
as anomalous microwave emission. Furthermore we model UCHII contributions using
data from the GHz CORNISH catalogue and reject this as the cause of the
GHz excess. Six known supernova remnants (SNR) are detected at GHz,
and we measure spectral indices consistent with the literature or show evidence
of steepening. The flux density of the SNR W44 at GHz is consistent with
a power-law extrapolation from lower frequencies with no indication of spectral
steepening in contrast with recent results from the Sardinia Radio Telescope.
We also extract five hydrogen radio recombination lines to map the warm ionized
gas, which can be used to estimate electron temperatures or to constrain
continuum free-free emission. The full COMAP Galactic plane survey, to be
released in 2023/2024, will be an invaluable resource for Galactic
astrophysics.Comment: Paper 6 of 7 in series. 28 pages, 10 figures, submitted to Ap
Generation and application of high power femtosecond pulses in the vibrational fingerprint region
Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)
Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic
Update on the safety of second generation antipsychotics in youths: a call for collaboration among paediatricians and child psychiatrists
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