366 research outputs found
Remote activated silver-zinc battery performance Interim report
Remote activated silver zinc battery performanc
Pegylated arginine deiminase drives arginine turnover and systemic autophagy to dictate energy metabolism
Obesity is a multi-systemic disorder of energy balance. Despite intense investigation, the determinants of energy homeostasis remain incompletely understood, and efficacious treatments against obesity and its complications are lacking. Here, we demonstrate that conferred arginine iminohydrolysis by the bacterial virulence factor and arginine deiminase
A survey for near-infrared H2 emission in Herbig Ae/Be stars: emission from the outer disks of HD 97048 and HD 100546
We report on a sensitive search for H2 1-0 S(1), 1-0 S(0) and 2-1 S(1)
ro-vibrational emission at 2.12, 2.22 and 2.25 micron in a sample of 15 Herbig
Ae/Be stars employing CRIRES, the ESO-VLT near-infrared high-resolution
spectrograph, at R~90,000. We detect the H2 1-0 S(1) line toward HD 100546 and
HD 97048. In the other 13 targets, the line is not detected. The H2 1-0 S(0)
and 2-1 S(1) lines are undetected in all sources. This is the first detection
of near-IR H2 emission in HD 100546. The H2 1-0 S(1) lines observed in HD
100546 and HD 97048 are observed at a velocity consistent with the rest
velocity of both stars, suggesting that they are produced in the circumstellar
disk. In HD 97048, the emission is spatially resolved and it is observed to
extend at least up to 200 AU. We report an increase of one order of magnitude
in the H2 1-0 S(1) line flux with respect to previous measurements taken in
2003 for this star, which suggests line variability. In HD 100546 the emission
is tentatively spatially resolved and may extend at least up to 50 AU. Modeling
of the H2 1-0 S(1) line profiles and their spatial extent with flat keplerian
disks shows that most of the emission is produced at a radius >5 AU. Upper
limits to the H2 1-0 S(0)/ 1-0 S(1) and H2 2-1 S(1)/1-0 S(1) line ratios in HD
97048 are consistent with H2 gas at T>2000 K and suggest that the emission
observed may be produced by X-ray excitation. The upper limits for the line
ratios for HD 100546 are inconclusive. Because the H2 emission is located at
large radii, for both sources a thermal emission scenario (i.e., gas heated by
collisions with dust) is implausible. We argue that the observation of H2
emission at large radii may be indicative of an extended disk atmosphere at
radii >5 AU. This may be explained by a hydrostatic disk in which gas and dust
are thermally decoupled or by a disk wind caused by photoevaporation.Comment: Accepted by A&A. 16 pages, 7 figure
Psychosocial effects of an Ebola outbreak at individual, community and international levels.
The 2013-2016 Ebola outbreak in Guinea, Liberia and Sierra Leone was the worst in history with over 28,000 cases and 11,000 deaths. Here we examine the psychosocial consequences of the epidemic. Ebola is a traumatic illness both in terms of symptom severity and mortality rates. Those affected are likely to experience psychological effects due to the traumatic course of the infection, fear of death and experience of witnessing others dying. Survivors can also experience psychosocial consequences due to feelings of shame or guilt (e.g. from transmitting infection to others) and stigmatization or blame from their communities. At the community level, a cyclical pattern of fear occurs, with a loss of trust in health services and stigma, resulting in disruptions of community interactions and community break down. Health systems in affected countries were severely disrupted and overstretched by the outbreak and their capacities were significantly reduced as almost 900 health-care workers were infected with Ebola and more than 500 died. The outbreak resulted in an increased need for health services, reduced quality of life and economic productivity and social system break down. It is essential that the global response to the outbreak considers both acute and long-term psychosocial needs of individuals and communities. Response efforts should involve communities to address psychosocial need, to rebuild health systems and trust and to limit stigma. The severity of this epidemic and its long-lasting repercussions should spur investment in and development of health systems
Barriers, attitudes, confidence, and knowledge of nurses regarding metabolic health screening and intervention in people with mental illness: a pilot study from Uganda
Background: People with mental illness are at an increased risk for
developing cardio-metabolic disorders. Routine screening following
pharmacotherapy is however unacceptably low in sub-Saharan African
countries with less than 1% adequately screened. It is unknown whether
this is due to a lack of adequate competences. Objectives: The aim of
this pilot study was to assess the barriers, attitudes, confidence, and
knowledge of nurses regarding metabolic health, prevention and
treatment in Uganda. Methods: Twenty-eight nurses (39% female,
30.9\ub16.9 years) completed the Metabolic \u2013 Barriers,
Confidence, Attitudes and Knowledge Questionnaire and the physical
activity prescription rate item of the Exercise in Mental Illness
Questionnaire. Results: More than 75% had a positive attitude towards
metabolic screening and intervention and more than 50% were confident
in providing smoking cessation advice, and physical activity and
nutritional counseling. However, 57% stated that their heavy workload
prevented them from doing health screening and promotion activities.
There was a negative correlation (\u3c1=-0.54, P=0.003) between the
frequency of physical activity prescription and the perception of the
inability of patients to change. Conclusion: The present findings
suggest that nurses are generally supportive of metabolic health
screening and intervention but their high workload prevents them from
implementing metabolic health interventions
Malic enzyme 1 absence in synovial sarcoma shifts antioxidant system dependence and increases sensitivity to ferroptosis induction with ACXT-3102
PURPOSE: To investigate the metabolism of synovial sarcoma (SS) and elucidate the effect of malic enzyme 1 absence on SS redox homeostasis.
EXPERIMENTAL DESIGN: ME1 expression was measured in SS clinical samples, SS cell lines, and tumors from an SS mouse model. The effect of ME1 absence on glucose metabolism was evaluated utilizing Seahorse assays, metabolomics, and C13 tracings. The impact of ME1 absence on SS redox homeostasis was evaluated by metabolomics, cell death assays with inhibitors of antioxidant systems, and measurements of intracellular reactive oxygen species (ROS). The susceptibility of ME1-null SS to ferroptosis induction was interrogated in vitro and in vivo.
RESULTS: ME1 absence in SS was confirmed in clinical samples, SS cell lines, and an SS tumor model. Investigation of SS glucose metabolism revealed that ME1-null cells exhibit higher rates of glycolysis and higher flux of glucose into the pentose phosphate pathway (PPP), which is necessary to produce NADPH. Evaluation of cellular redox homeostasis demonstrated that ME1 absence shifts dependence from the glutathione system to the thioredoxin system. Concomitantly, ME1 absence drives the accumulation of ROS and labile iron. ROS and iron accumulation enhances the susceptibility of ME1-null cells to ferroptosis induction with inhibitors of xCT (erastin and ACXT-3102). In vivo xenograft models of ME1-null SS demonstrate significantly increased tumor response to ACXT-3102 compared with ME1-expressing controls.
CONCLUSIONS: These findings demonstrate the translational potential of targeting redox homeostasis in ME1-null cancers and establish the preclinical rationale for a phase I trial of ACXT-3102 in SS patients. See related commentary by Subbiah and Gan, p. 3408
Spatial and temporal melt variability at Helheim Glacier, East Greenland, and its effect on ice dynamics
This is the publisher's version, also available electronically from "http://onlinelibrary.wiley.com".[1] Understanding the behavior of large outlet glaciers draining the Greenland Ice Sheet is critical for assessing the impact of climate change on sea level rise. The flow of marine-terminating outlet glaciers is partly governed by calving-related processes taking place at the terminus but is also influenced by the drainage of surface runoff to the bed through moulins, cracks, and other pathways. To investigate the extent of the latter effect, we develop a distributed surface-energy-balance model for Helheim Glacier, East Greenland, to calculate surface melt and thereby estimate runoff. The model is driven by data from an automatic weather station operated on the glacier during the summers of 2007 and 2008, and calibrated with independent measurements of ablation. Modeled melt varies over the deployment period by as much as 68% relative to the mean, with melt rates approximately 77% higher on the lower reaches of the glacier trunk than on the upper glacier. We compare melt variations during the summer season to estimates of surface velocity derived from global positioning system surveys. Near the front of the glacier, there is a significant correlation (on >95% levels) between variations in runoff (estimated from surface melt) and variations in velocity, with a 1 day delay in velocity relative to melt. Although the velocity changes are small compared to accelerations previously observed following some calving events, our findings suggest that the flow speed of Helheim Glacier is sensitive to changes in runoff. The response is most significant in the heavily crevassed, fast-moving region near the calving front. The delay in the peak of the cross-correlation function implies a transit time of 12–36 h for surface runoff to reach the bed
Discovery and targeting of a noncanonical mechanism of sarcoma resistance to ADI-PEG20 mediated by the microenvironment
PURPOSE: Many cancers lack argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme of arginine biosynthesis. This deficiency causes arginine auxotrophy, targetable by extracellular arginine-degrading enzymes such as ADI-PEG20. Long-term tumor resistance has thus far been attributed solely to ASS1 reexpression. This study examines the role of ASS1 silencing on tumor growth and initiation and identifies a noncanonical mechanism of resistance, aiming to improve clinical responses to ADI-PEG20.
EXPERIMENTAL DESIGN: Tumor initiation and growth rates were measured for a spontaneous Ass1 knockout (KO) murine sarcoma model. Tumor cell lines were generated, and resistance to arginine deprivation therapy was studied in vitro and in vivo.
RESULTS: Conditional Ass1 KO affected neither tumor initiation nor growth rates in a sarcoma model, contradicting the prevalent idea that ASS1 silencing confers a proliferative advantage. Ass1 KO cells grew robustly through arginine starvation in vivo, while ADI-PEG20 remained completely lethal in vitro, evidence that pointed toward a novel mechanism of resistance mediated by the microenvironment. Coculture with Ass1-competent fibroblasts rescued growth through macropinocytosis of vesicles and/or cell fragments, followed by recycling of protein-bound arginine through autophagy/lysosomal degradation. Inhibition of either macropinocytosis or autophagy/lysosomal degradation abrogated this growth support effect in vitro and in vivo.
CONCLUSIONS: Noncanonical, ASS1-independent tumor resistance to ADI-PEG20 is driven by the microenvironment. This mechanism can be targeted by either the macropinocytosis inhibitor imipramine or the autophagy inhibitor chloroquine. These safe, widely available drugs should be added to current clinical trials to overcome microenvironmental arginine support of tumors and improve patient outcomes
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