Ferrous iron formed during microbial ferric iron reduction induces phase transformations of poorly crystalline into more crystalline and thermodynamically more stable iron (oxyhydr)oxides. Yet, ...characterizing the resulting decreases in the reactivity of the remaining oxide ferric iron toward reduction (i.e., its reducibility) has been challenging. Here, we used the reduction of six-line ferrihydrite by Shewanella oneidensis MR-1 as a model system to demonstrate that mediated electrochemical reduction (MER) allows directly following decreases in oxide ferric iron reducibility during the transformation of ferrihydrite into goethite and magnetite which we characterized by X-ray diffraction analysis and transmission electron microscopy imaging. Ferrihydrite was fully reducible in MER at both pHMER of 5.0 and 7.5. Decreases in iron oxide reducibility associated with ferrihydrite transformation into magnetite were accessible at both pHMER because the formed magnetite was not reducible under either of these conditions. Conversely, decreases in iron oxide reducibility associated with goethite formation were apparent only at the highest tested pHMER of 7.5 and thus the thermodynamically least favorable conditions for iron oxide reductive dissolution. The unique capability to adjust the thermodynamic boundary conditions in MER to the specific reducibilities of individual iron (oxyhydr)oxides makes this electrochemical approach broadly applicable for studying changes in iron oxide reducibility in heterogeneous environmental samples such as soils and sediments.
Bacteria surround themselves with cell walls to maintain cell rigidity and protect against environmental insults. Here we review chemical and biochemical techniques employed to study bacterial cell ...wall biogenesis. Recent advances including the ability to isolate critical intermediates, metabolic approaches for probe incorporation and isotopic labeling techniques have provided critical insight into the biochemistry of cell walls. Fundamental manuscripts that have used these techniques to discover cell wall interacting proteins, flippases and cell wall stoichiometry are discussed in detail. The review highlights that these powerful methods and techniques have exciting potential to identify and characterize new targets for antibiotic development.
Evolutionary conservation is an invaluable tool for inferring functional significance in the genome, including regions that are crucial across many species and those that have undergone convergent ...evolution. Computational methods to test for sequence conservation are dominated by algorithms that examine the ability of one or more nucleotides to align across large evolutionary distances. While these nucleotide alignment-based approaches have proven powerful for protein-coding genes and some non-coding elements, they fail to capture conservation of many enhancers, distal regulatory elements that control spatial and temporal patterns of gene expression. The function of enhancers is governed by a complex, often tissue- and cell type-specific code that links combinations of transcription factor binding sites and other regulation-related sequence patterns to regulatory activity. Thus, function of orthologous enhancer regions can be conserved across large evolutionary distances, even when nucleotide turnover is high.
We present a new machine learning-based approach for evaluating enhancer conservation that leverages the combinatorial sequence code of enhancer activity rather than relying on the alignment of individual nucleotides. We first train a convolutional neural network model that can predict tissue-specific open chromatin, a proxy for enhancer activity, across mammals. Next, we apply that model to distinguish instances where the genome sequence would predict conserved function versus a loss of regulatory activity in that tissue. We present criteria for systematically evaluating model performance for this task and use them to demonstrate that our models accurately predict tissue-specific conservation and divergence in open chromatin between primate and rodent species, vastly out-performing leading nucleotide alignment-based approaches. We then apply our models to predict open chromatin at orthologs of brain and liver open chromatin regions across hundreds of mammals and find that brain enhancers associated with neuron activity have a stronger tendency than the general population to have predicted lineage-specific open chromatin.
The framework presented here provides a mechanism to annotate tissue-specific regulatory function across hundreds of genomes and to study enhancer evolution using predicted regulatory differences rather than nucleotide-level conservation measurements.
ABSTRACT
HiPERCAM is a portable, quintuple-beam optical imager that saw first light on the 10.4-m Gran Telescopio Canarias (GTC) in 2018. The instrument uses re-imaging optics and four dichroic ...beamsplitters to record $u_{\rm s}\, g_{\rm s}\, r_{\rm s}\, i_{\rm s}\, z_{\rm s}$ (320–1060 nm) images simultaneously on its five CCD cameras, each of 3.1-arcmin (diagonal) field of view. The detectors in HiPERCAM are frame-transfer devices cooled thermo-electrically to 183 K, thereby allowing both long-exposure, deep imaging of faint targets, as well as high-speed (over 1000 windowed frames per second) imaging of rapidly varying targets. A comparison-star pick-off system in the telescope focal plane increases the effective field of view to 6.7 arcmin for differential photometry. Combining HiPERCAM with the world’s largest optical telescope enables the detection of astronomical sources to gs ∼ 23 in 1 s and gs ∼ 28 in 1 h. In this paper, we describe the scientific motivation behind HiPERCAM, present its design, report on its measured performance, and outline some planned enhancements.
This study aimed to investigate whether supplementation with 12 mg⋅day−1 astaxanthin for 7 days can improve exercise performance and metabolism during a 40 km cycling time trial.
A randomised, ...double-blind, crossover design was employed.
Twelve recreationally trained male cyclists (VO2peak: 56.5 ± 5.5 mL⋅kg−1⋅min−1, Wmax: 346.8 ± 38.4 W) were recruited. Prior to each experimental trial, participants were supplemented with either 12 mg⋅day−1 astaxanthin or an appearance-matched placebo for 7 days (separated by 14 days of washout). On day 7 of supplementation, participants completed a 40 km cycling time trial on a cycle ergometer, with indices of exercise metabolism measured throughout.
Time to complete the 40 km cycling time trial was improved by 1.2 ± 1.7% following astaxanthin supplementation, from 70.76 ± 3.93 min in the placebo condition to 69.90 ± 3.78 min in the astaxanthin condition (mean improvement = 51 ± 71 s, p = 0.029, g = 0.21). Whole-body fat oxidation rates were also greater (+0.09 ± 0.13 g⋅min−1, p = 0.044, g = 0.52), and the respiratory exchange ratio lower (−0.03 ± 0.04, p = 0.024, g = 0.60) between 39–40 km in the astaxanthin condition.
Supplementation with 12 mg⋅day−1 astaxanthin for 7 days provided an ergogenic benefit to 40 km cycling time trial performance in recreationally trained male cyclists and enhanced whole-body fat oxidation rates in the final stages of this endurance-type performance event.
Parkinson's disease (PD) is characterized pathologically by intraneuronal inclusions called Lewy bodies, largely comprised of α-synuclein. Multiplication of the α-synuclein gene locus increases ...α-synuclein expression and causes PD. Thus, overexpression of wild-type α-synuclein is toxic. In this study, we demonstrate that α-synuclein overexpression impairs macroautophagy in mammalian cells and in transgenic mice. Our data show that α-synuclein compromises autophagy via Rab1a inhibition and Rab1a overexpression rescues the autophagy defect caused by α-synuclein. Inhibition of autophagy by α-synuclein overexpression or Rab1a knockdown causes mislocalization of the autophagy protein, Atg9, and decreases omegasome formation. Rab1a, α-synuclein, and Atg9 all regulate formation of the omegasome, which marks autophagosome precursors.
Introduction
Cystic fibrosis (CF) treatment has increasingly focused on highly effective modulators. Despite measurable benefits of modulators, there is little guidance for CF care team members on ...providing education and support to patients regarding initiation of these therapies. We aimed to explore patient, caregiver, and clinician perceptions of modulators and influences on decisions about starting cystic fibrosis transmembrane regulator (CFTR) modulators.
Methods
We conducted semistructured interviews with CF clinicians, adults with CF, and caregivers of children with CF. We reviewed audio recordings and coded responses to identify central themes.
Results
We interviewed 8 CF clinicians, 9 adults with CF, and 11 caregivers of children with CF. Themes centered on emotional responses to modulator availability, influences on decision‐making, concerns about side effects, impact of modulators on planning for the future, the benefits of the multidisciplinary CF care team in supporting treatment decisions, and the unique needs of people with CF who are not eligible for modulators. Clinicians described changes in conversations about modulators since the approval of elexacaftor/tezacaftor/ivacaftor, specifically greater willingness to prescribe with less nuanced conversations with patients and/or caregivers regarding their use.
Conclusion
Based on perspectives and experiences of CF clinicians, adults with CF, and caregivers of children with CF, we suggest clinicians approach conversations about CFTR modulators thoughtfully and thoroughly, utilizing the multidisciplinary model of CF care in exploring patient and caregiver emotions while filling in knowledge gaps, asking about treatment goals beyond potential clinical benefit, and having compassionate conversations with those who are ineligible for modulators.
•Upgrading by Pd-biomagnetite comparable to commercial alumina supported catalysts.•Higher liquid yield using Pd-biomagnetite versus alumina based catalysts.•Significant reduction in coke levels ...using Pd-biomagnetite.•Potential for ‘green’ biosynthesis of Pd-biomagnetite.
In situ catalytic upgrading of heavy oil offers significant cost savings and overcomes logistical challenges associated with the high viscosity, low API gravity and high molecular weight fractions of unconventional hydrocarbon resources. The THAI-CAPRI process (toe-to-heel air injection – catalytic upgrading process in situ) offers one such route to upgrading through the use of high surface area transition metal cracking catalysts surrounding the production well. Here, we describe the catalytic upgrading of heavy oil in a stirred batch reactor by a biogenic nanoscale magnetite (BnM; Fe3O4). A 97.8% decrease in viscosity relative to the feed oil was achieved and coking was lower compared to thermal cracking alone (6.9wt% versus 10.2wt%). The activity of this catalyst was further enhanced by a simple one-step addition of surface associated Pd to achieve loadings of 4.3, 7.1 and 9.5wt% Pd. This led to significant decreases in viscosity of up to 99.4% for BnM loaded with 9.5wt% Pd. An increment of 7.8° in API gravity with respect to the feed oil was achieved for 9.5wt% Pd-BnM, compared with thermal cracking alone (5.3°). Whilst this level of upgrading was comparable to commercially available and previously tested catalysts, significant decreases in the coke content (3wt% for 9.5wt% Pd-BnM versus 10wt% for thermal cracking) and associated increases in liquid content (∼90wt% for 9.5wt% Pd-BnM versus ∼79wt% for thermal cracking) demonstrate the potential for the use of Pd-augmented biogenic magnetite as a catalyst in the THAI CAPRI process.
Neonatal herpes most commonly results from fetal exposure to infected maternal genital secretions at the time of delivery. The risk of transmission from mother to infant as it relates to maternal ...herpes simplex virus (HSV) serologic status and exposure to HSV in the maternal genital tract at the time of labor has not been quantified. Furthermore, no data exist on whether cesarean delivery, the standard of care for women with genital herpes lesions at the time of delivery, reduces HSV transmission.
To determine the effects of viral shedding, maternal HSV serologic status, and delivery route on the risk of transmission of HSV from mother to infant.
Prospective cohort of pregnant women enrolled between January 1982 and December 1999.
A university medical center, a US Army medical center, and 5 community hospitals in Washington State.
A total of 58 362 pregnant women, of whom 40 023 had HSV cultures obtained from the cervix and external genitalia and 31 663 had serum samples tested for HSV.
Rates of neonatal HSV infection.
Among the 202 women from whom HSV was isolated at the time of labor, 10 (5%) had neonates with HSV infection (odds ratio OR, 346; 95% confidence interval CI, 125-956 for neonatal herpes when HSV was isolated vs not isolated). Cesarean delivery significantly reduced the HSV transmission rate among women from whom HSV was isolated (1 1.2% of 85 cesarean vs 9 7.7% of 117 vaginal; OR, 0.14; 95% CI, 0.02-1.08; P =.047). Other risk factors for neonatal HSV included first-episode infection (OR, 33.1; 95% CI, 6.5-168), HSV isolation from the cervix (OR, 32.6; 95% CI, 4.1-260), HSV-1 vs HSV-2 isolation at the time of labor (OR, 16.5; 95% CI, 4.1-65), invasive monitoring (OR, 6.8; 95% CI, 1.4-32), delivery before 38 weeks (OR, 4.4; 95% CI, 1.2-16), and maternal age less than 21 years (OR, 4.1; 95% CI, 1.1-15). Neonatal HSV infection rates per 100 000 live births were 54 (95% CI, 19.8-118) among HSV-seronegative women, 26 (95% CI, 9.3-56) among women who were HSV-1-seropositive only, and 22 (95% CI, 4.4-64) among all HSV-2-seropositive women.
Neonatal HSV infection rates can be reduced by preventing maternal acquisition of genital HSV-1 and HSV-2 infection near term. It can also be reduced by cesarean delivery and limiting the use of invasive monitors among women shedding HSV at the time of labor.
Abstract
The paucity of hypervelocity stars (HVSs) known to date has severely hampered their potential to investigate the stellar population of the Galactic Centre and the Galactic potential. The ...first Gaia data release (DR1, 2016 September 14) gives an opportunity to increase the current sample. The challenge is the disparity between the expected number of HVSs and that of bound background stars. We have applied a novel data mining algorithm based on machine learning techniques, an artificial neural network, to the Tycho–Gaia astrometric solution catalogue. With no pre-selection of data, we could exclude immediately ∼99 per cent of the stars in the catalogue and find 80 candidates with more than 90 per cent predicted probability to be HVSs, based only on their position, proper motions and parallax. We have cross-checked our findings with other spectroscopic surveys, determining radial velocities for 30 and spectroscopic distances for five candidates. In addition, follow-up observations have been carried out at the Isaac Newton Telescope for 22 stars, for which we obtained radial velocities and distance estimates. We discover 14 stars with a total velocity in the Galactic rest frame >400 km s−1, and five of these have a probability of >50 per cent of being unbound from the Milky Way. Tracing back their orbits in different Galactic potential models, we find one possible unbound HVS with v ∼ 520 km s−1, five bound HVSs and, notably, five runaway stars with median velocity between 400 and 780 km s−1. At the moment, uncertainties in the distance estimates and ages are too large to confirm the nature of our candidates by narrowing down their ejection location, and we wait for future Gaia releases to validate the quality of our sample. This test successfully demonstrates the feasibility of our new data-mining routine.
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