Multiple roles of reactive oxygen species (ROS) and their consequences for health and disease are emerging throughout biological sciences. This development has led researchers unfamiliar with the ...complexities of ROS and their reactions to employ commercial kits and probes to measure ROS and oxidative damage inappropriately, treating ROS (a generic abbreviation) as if it were a discrete molecular entity. Unfortunately, the application and interpretation of these measurements are fraught with challenges and limitations. This can lead to misleading claims entering the literature and impeding progress, despite a well-established body of knowledge on how best to assess individual ROS, their reactions, role as signalling molecules and the oxidative damage that they can cause. In this consensus statement we illuminate problems that can arise with many commonly used approaches for measurement of ROS and oxidative damage, and propose guidelines for best practice. We hope that these strategies will be useful to those who find their research requiring assessment of ROS, oxidative damage and redox signalling in cells and in vivo.
Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims of this study were to determine ...the frequency of different genes in a large cohort of patients with CMT and devise guidelines for genetic testing in practice.
The genes known to cause CMT were sequenced in 1607 patients with CMT (425 patients attending an inherited neuropathy clinic and 1182 patients whose DNA was sent to the authors for genetic testing) to determine the proportion of different subtypes in a UK population.
A molecular diagnosis was achieved in 62.6% of patients with CMT attending the inherited neuropathy clinic; in 80.4% of patients with CMT1 (demyelinating CMT) and in 25.2% of those with CMT2 (axonal CMT). Mutations or rearrangements in PMP22, GJB1, MPZ and MFN2 accounted for over 90% of the molecular diagnoses while mutations in all other genes tested were rare.
Four commonly available genes account for over 90% of all CMT molecular diagnoses; a diagnostic algorithm is proposed based on these results for use in clinical practice. Any patient with CMT without a mutation in these four genes or with an unusual phenotype should be considered for referral for an expert opinion to maximise the chance of reaching a molecular diagnosis.
The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis ...(hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome.
We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up.
Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval CI, 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups.
Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT ClinicalTrials.gov number, NCT00790335 .).
Unconventional Fermi surface in an insulating state Tan, B. S.; Hsu, Y.-T.; Zeng, B. ...
Science (American Association for the Advancement of Science),
07/2015, Letnik:
349, Številka:
6245
Journal Article
Recenzirano
Odprti dostop
Insulators occur in more than one guise; a recent finding was a class of topological insulators, which host a conducting surface juxtaposed with an insulating bulk. Here, we report the observation of ...an unusual insulating state with an electrically insulating bulk that simultaneously yields bulk quantum oscillations with characteristics of an unconventional Fermi liquid. We present quantum oscillation measurements of magnetic torque in high-purity single crystals of the Kondo insulator SmB6, which reveal quantum oscillation frequencies characteristic of a large three-dimensional conduction electron Fermi surface similar to the metallic rare earth hexaborides such as PrB6 and LaB6. The quantum oscillation amplitude strongly increases at low temperatures, appearing strikingly at variance with conventional metallic behavior.
We use 2005-2009 satellite observations of formaldehyde (HCHO) columns from the OMI instrument to infer biogenic isoprene emissions at monthly 1 × 1° resolution over the African continent. Our work ...includes new approaches to remove biomass burning influences using OMI absorbing aerosol optical depth data (to account for transport of fire plumes) and anthropogenic influences using AATSR satellite data for persistent small-flame fires (gas flaring). The resulting biogenic HCHO columns (Ω
) from OMI follow closely the distribution of vegetation patterns in Africa. We infer isoprene emission (
) from the local sensitivity
= ΔΩ
/ Δ
derived with the GEOS-Chem chemical transport model using two alternate isoprene oxidation mechanisms, and verify the validity of this approach using AMMA aircraft observations over West Africa and a longitudinal transect across central Africa. Displacement error (smearing) is diagnosed by anomalously high values of
and the corresponding data are removed. We find significant sensitivity of
to NO
under low-NO
conditions that we fit to a linear function of tropospheric column NO
. We estimate a 40% error in our inferred isoprene emissions under high-NO
conditions and 40-90% under low-NO
conditions. Our results suggest that isoprene emission from the central African rainforest is much lower than estimated by the state-of-the-science MEGAN inventory.
Wintertime ammonium nitrate aerosol pollution is a severe air quality issue affecting both developed and rapidly urbanizing regions from Europe to East Asia. In the United States, it is acute in ...western basins subject to inversions that confine pollutants near the surface. Measurements and modeling of a wintertime pollution episode in Salt Lake Valley, Utah, demonstrate that ammonium nitrate is closely related to photochemical ozone through a common parameter, total odd oxygen, Ox,total. We show that the traditional nitrogen oxide and volatile organic compound (NOx‐VOC) framework for evaluating ozone mitigation strategies also applies to ammonium nitrate. Despite being nitrate‐limited, ammonium nitrate aerosol pollution in Salt Lake Valley is responsive to VOCs control and, counterintuitively, not initially responsive to NOx control. We demonstrate simultaneous nitrate limitation and NOx saturation and suggest this phenomenon may be general. This finding may identify an unrecognized control strategy to address a global public health issue in regions with severe winter aerosol pollution.
Plain Language Summary
Particulate matter (PM) is dangerous to human health and impacts visibility and climate. In the United States, Europe, and Asia, PM is severe in urban areas in the winter when ammonium nitrate, NH4NO3, comprises an appreciable fraction of the total PM mass. A key control strategy is to reduce emissions of the limiting reagent. Using measurements from a recent field campaign in the Salt Lake Valley, Utah, which experiences high PM levels in winter, we demonstrate that emission control strategies can be evaluated using the same framework commonly used to control ozone, another common pollutant that occurs at high levels in urban areas in the summer. We show that initial control of the NOx precursor is ineffective at reducing NH4NO3 aerosol in the Salt Lake Valley, while initial control of volatile organic compounds, which are not a direct precursor for either nitrate or ammonium, is effective due to their influence on oxidation cycles. This finding differs from many mitigation strategies in the western United States and may also be relevant to other regions in Europe and Asia which experience high wintertime PM.
Key Points
Wintertime ammonium nitrate aerosol pollution is closely tied to photochemical ozone production through a common parameter, Ox,total
Box modeling reveals ammonium nitrate formation in the Salt Lake Valley is nitrate‐limited but NOx‐saturated
Mitigation strategies that focus on NOx control in some wintertime‐polluted layers may initially increase ammonium nitrate
To understand the origin of superconductivity, it is crucial to ascertain the nature and origin of the primary carriers available to participate in pairing. Recent quantum oscillation experiments on ...high-transition-temperature (high-T(c)) copper oxide superconductors have revealed the existence of a Fermi surface akin to that in normal metals, comprising fermionic carriers that undergo orbital quantization. The unexpectedly small size of the observed carrier pocket, however, leaves open a variety of possibilities for the existence or form of any underlying magnetic order, and its relation to d-wave superconductivity. Here we report experiments on quantum oscillations in the magnetization (the de Haas-van Alphen effect) in superconducting YBa(2)Cu(3)O(6.51) that reveal more than one carrier pocket. In particular, we find evidence for the existence of a much larger pocket of heavier mass carriers playing a thermodynamically dominant role in this hole-doped superconductor. Importantly, characteristics of the multiple pockets within this more complete Fermi surface impose constraints on the wavevector of any underlying order and the location of the carriers in momentum space. These constraints enable us to construct a possible density-wave model with spiral or related modulated magnetic order, consistent with experimental observations.
Families of children with congenital heart disease (CHD) cope differently depending on individual and familial factors beyond the severity of the child’s condition. Recent research has shifted from ...an emphasis on the psychopathology of family functioning to a focus on the resilience of families in coping with the challenges presented by a young child’s condition. The increasing number of studies on the relationship between psychological adaptation, parental coping and parenting practices and quality of life in families of children with CHD necessitates an in-depth re-exploration. The present study reviews published literature in this area over the past 25 years to generate evidence to inform clinical practice, particularly to better target parent and family interventions designed to enhance family coping. Twenty-five studies were selected for inclusion, using the PRISMA guidelines. Thematic analysis identified a number of themes including psychological distress and well-being, gender differences in parental coping, and variable parenting practices and a number of subthemes. There is general agreement in the literature that families who have fewer psychosocial resources and lower levels of support may be at risk of higher psychological distress and lower well-being over time, for both parent and the child. Moreover, familial factors such as cohesiveness and adaptive parental coping strategies are necessary for successful parental adaptation to CHD in their child. The experiences, needs and ways of coping in families of children with CHD are diverse and multi-faceted. A holistic approach to early psychosocial intervention should target improved adaptive coping and enhanced productive parenting practices in this population. This should lay a strong foundation for these families to successfully cope with future uncertainties and challenges at various phases in the trajectory of the child’s condition.
Obtaining a burning plasma is a critical step towards self-sustaining fusion energy
. A burning plasma is one in which the fusion reactions themselves are the primary source of heating in the plasma, ...which is necessary to sustain and propagate the burn, enabling high energy gain. After decades of fusion research, here we achieve a burning-plasma state in the laboratory. These experiments were conducted at the US National Ignition Facility, a laser facility delivering up to 1.9 megajoules of energy in pulses with peak powers up to 500 terawatts. We use the lasers to generate X-rays in a radiation cavity to indirectly drive a fuel-containing capsule via the X-ray ablation pressure, which results in the implosion process compressing and heating the fuel via mechanical work. The burning-plasma state was created using a strategy to increase the spatial scale of the capsule
through two different implosion concepts
. These experiments show fusion self-heating in excess of the mechanical work injected into the implosions, satisfying several burning-plasma metrics
. Additionally, we describe a subset of experiments that appear to have crossed the static self-heating boundary, where fusion heating surpasses the energy losses from radiation and conduction. These results provide an opportunity to study α-particle-dominated plasmas and burning-plasma physics in the laboratory.
Through collaboration with Inuit hunters, we examined the stomach contents of 142 seals (ringed seals Phoca hispida; n = 135, bearded seals Erignathus barbatus; n = 6, and one harbour seal Phoca ...vitualina; n = 1) hunted between 2007 and 2019 from communities around Nunavut to assess whether seals in the eastern Canadian Arctic ingest and retain plastics in their stomachs. The seals in this study ranged from juveniles to adults of up to 30 years of age, and 55% of the seals were males. We found no evidence of plastic ingestion in any of the seals suggesting that seals in Nunavut are not accumulating plastics (>425 μm) in their stomachs. These data provide important baseline information for future plastic pollution monitoring programs in the Arctic.
•Stomach contents of 142 seals from Nunavut examined for plastics >425 μm•No evidence of plastic pollution was found in any of the seal stomachs.•These data provide baseline information for future Arctic monitoring programs.
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