2,802 research outputs found
Evidence that oxidative stress is increased in patients with X-linked adrenoleukodystrophy
AbstractX-linked adrenoleukodystrophy (X-ALD) is a hereditary disorder of peroxisomal metabolism biochemically characterized by the accumulation of very long chain fatty acids (VLCFA), particularly hexacosanoic acid (C26:0) and tetracosanoic acid (C24:0) in different tissues and in biological fluids. The disease is clinically characterized by central and peripheral demyelination and adrenal insufficiency, which is closely related to the increased concentrations of these fatty acids. However, the mechanisms underlying the brain damage in X-ALD are poorly known. Considering that free radical generation is involved in various neurodegererative disorders, like Parkinson disease, multiple sclerosis and Alzheimer's disease, in the present study we evaluated various oxidative stress parameters, namely chemiluminescence, thiobarbituric acid reactive species (TBA-RS), total radical-trapping antioxidant potential (TRAP), and total antioxidant reactivity (TAR) in plasma of X-ALD patients, as well as the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in erythrocytes and fibroblasts from these patients. It was verified a significant increase of plasma chemiluminescence and TBA-RS, reflecting induction of lipid peroxidation, as well as a decrease of plasma TAR, indicating a deficient capacity to rapidly handle an increase of reactive species. We also observed a significant increase of erythrocytes GPx activity and of catalase and SOD activities in fibroblasts from the patients studied. It is therefore proposed that oxidative stress may be involved in pathophysiology of X-ALD
Myocardial ultrasonic tissue characterization in patients with thyroid dysfunction
<p>Abstract</p> <p>Background</p> <p>Structural myocardial abnormalities have been extensively documented in hypothyroidism. Experimental studies in animal models have also shown involvement of thyroid hormones in gene expression of myocardial collagen. This study was planned to investigate the ability of ultrasonic tissue characterization, as evaluated by integrated backscatter (IBS), to early identify myocardial involvement in thyroid dysfunction.</p> <p>Patients and Methods</p> <p>We studied 15 patients with hyperthyroidism (HYPER), 8 patients with hypothyroidism (HYPO), 14 patients with subclinical hypothyroidism (SCH) and 19 normal (N) subjects, who had normal LV systolic function. After treatment, 10 HYPER, 6 HYPO, and 8 SCH patients were reevaluated. IBS images were obtained and analyzed in parasternal short axis (papillary muscle level) view, at left ventricular (LV) posterior wall. The following IBS variables were analyzed: 1) the corrected coefficient (CC) of IBS, obtained by dividing IBS intensity by IBS intensity measured in a rubber phantom, using the same equipment adjustments, at the same depth; 2) cardiac cyclic variation (CV) of IBS - peak-to-peak difference between maximal and minimal values of IBS during cardiac cycle; 3) cardiac cyclic variation index (CVI) of IBS - percentual relationship between the cyclic variation (CV) and the mean value of IBS intensity.</p> <p>Results</p> <p>CC of IBS was significantly larger (p < 0.05) in HYPER (1.57 ± 0.6) and HYPO (1.53 ± 0.3) as compared to SCH (1.32 ± 0.3) or N (1.15 ± 0.27). The CV (dB) (HYPO: 7.5 ± 2.4; SCH: 8.2 ± 3.1; HYPER: 8.2 ± 2.0) and the CVI (HYPO: 35.6 ± 19.7%; SCH: 34.7 ± 17.5%; HYPER: 37.8 ± 11.6%) were not significantly different in patients with thyroid dysfunction as compared to N (7.0 ± 2.0 and 44.5 ± 15.1%).</p> <p>Conclusions</p> <p>CC of IBS was able to differentiate cardiac involvement in patients with overt HYPO and HYPER who had normal LV systolic function. These early myocardial structural abnormalities were partially reversed by drug therapy in HYPER group. On the other hand, although mean IBS intensity tended to be slightly larger in patients with SCH as compared to N, this difference was not statistical significant.</p
Drosophila Neurotrophins Reveal a Common Mechanism for Nervous System Formation
Neurotrophic interactions occur in Drosophila, but to date, no neurotrophic factor had been found. Neurotrophins are the main vertebrate secreted signalling molecules that link nervous system structure and function: they regulate
neuronal survival, targeting, synaptic plasticity, memory and cognition. We have identified a neurotrophic factor in
flies, Drosophila Neurotrophin (DNT1), structurally related to all known neurotrophins and highly conserved in insects.By investigating with genetics the consequences of removing DNT1 or adding it in excess, we show that DNT1
maintains neuronal survival, as more neurons die in DNT1 mutants and expression of DNT1 rescues naturally occurring
cell death, and it enables targeting by motor neurons. We show that Spa¨ tzle and a further fly neurotrophin superfamily member, DNT2, also have neurotrophic functions in flies. Our findings imply that most likely a neurotrophin was present in the common ancestor of all bilateral organisms, giving rise to invertebrate and vertebrate neurotrophins through gene or whole-genome duplications. This work provides a missing link between aspects of neuronal function in flies and vertebrates, and it opens the opportunity to use Drosophila to investigate further aspects of neurotrophin function and to model related diseases
Scalable Reinforcement-Learning-Based Neural Architecture Search for Cancer Deep Learning Research
Cancer is a complex disease, the understanding and treatment of which are
being aided through increases in the volume of collected data and in the scale
of deployed computing power. Consequently, there is a growing need for the
development of data-driven and, in particular, deep learning methods for
various tasks such as cancer diagnosis, detection, prognosis, and prediction.
Despite recent successes, however, designing high-performing deep learning
models for nonimage and nontext cancer data is a time-consuming,
trial-and-error, manual task that requires both cancer domain and deep learning
expertise. To that end, we develop a reinforcement-learning-based neural
architecture search to automate deep-learning-based predictive model
development for a class of representative cancer data. We develop custom
building blocks that allow domain experts to incorporate the
cancer-data-specific characteristics. We show that our approach discovers deep
neural network architectures that have significantly fewer trainable
parameters, shorter training time, and accuracy similar to or higher than those
of manually designed architectures. We study and demonstrate the scalability of
our approach on up to 1,024 Intel Knights Landing nodes of the Theta
supercomputer at the Argonne Leadership Computing Facility.Comment: SC '19: IEEE/ACM International Conference on High Performance
Computing, Networking, Storage and Analysis, November 17--22, 2019, Denver,
C
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Uncoupling human and climate drivers of late Holocene vegetation change in southern Brazil
In the highlands of southern Brazil an anthropogenitcally driven expansion of forest occurred at the
expense of grasslands between 1410 and 900cal BP, coincident with a period of demographic and
cultural change in the region. Previous studies have debated the relative contributions of increasing
wetter and warmer climate conditions and human landscape modifcations to forest expansion, but
generally lacked high resoltiuon proxies to measure these efects, or have relied on single proxies to
reconstruct both climate and vegetation. Here, we develop and test a model of natural ecosystem
distribution against vegetation histories, paleoclimate proxies, and the archaeological record to
distinguish human from temperature and precipitation impacts on the distribution and expansion of
Araucaria forests during the late Holocene. Carbon isotopes from soil profles confrm that in spite of
climatic fuctuations, vegetation was stable and forests were spatially limited to south-facing slopes
in the absence of human inputs. In contrast, forest management strategies for the past 1400 years
expanded this economically important forest beyond its natural geographic boundaries in areas of
dense pre-Columbian occupation, suggesting that landscape modifcations were linked to demographic
changes, the efects of which are still visible today
Measurement of the cross-section and charge asymmetry of bosons produced in proton-proton collisions at TeV with the ATLAS detector
This paper presents measurements of the and cross-sections and the associated charge asymmetry as a
function of the absolute pseudorapidity of the decay muon. The data were
collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with
the ATLAS experiment at the LHC and correspond to a total integrated luminosity
of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements
varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the
1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured
with an uncertainty between 0.002 and 0.003. The results are compared with
predictions based on next-to-next-to-leading-order calculations with various
parton distribution functions and have the sensitivity to discriminate between
them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables,
submitted to EPJC. All figures including auxiliary figures are available at
https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13
Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector
A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13 TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV
Multiwavelength studies of MHD waves in the solar chromosphere: An overview of recent results
The chromosphere is a thin layer of the solar atmosphere that bridges the
relatively cool photosphere and the intensely heated transition region and
corona. Compressible and incompressible waves propagating through the
chromosphere can supply significant amounts of energy to the interface region
and corona. In recent years an abundance of high-resolution observations from
state-of-the-art facilities have provided new and exciting ways of
disentangling the characteristics of oscillatory phenomena propagating through
the dynamic chromosphere. Coupled with rapid advancements in
magnetohydrodynamic wave theory, we are now in an ideal position to thoroughly
investigate the role waves play in supplying energy to sustain chromospheric
and coronal heating. Here, we review the recent progress made in
characterising, categorising and interpreting oscillations manifesting in the
solar chromosphere, with an impetus placed on their intrinsic energetics.Comment: 48 pages, 25 figures, accepted into Space Science Review
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
Mutation and deletion analysis of GFRα-1, encoding the co-receptor for the GDNF/RET complex, in human brain tumours
Glial cell line-derived neurotrophic factor (GDNF) plays a key role in the control of vertebrate neuron survival and differentiation in both the central and peripheral nervous systems. GDNF preferentially binds to GFRα-1 which then interacts with the receptor tyrosine kinase RET. We investigated a panel of 36 independent cases of mainly advanced sporadic brain tumours for the presence of mutations in GDNF and GFRα-1. No mutations were found in the coding region of GDNF. We identified six previously described GFRα-1 polymorphisms, two of which lead to an amino acid change. In 15 of 36 brain tumours, all polymorphic variants appeared to be homozygous. Of these 15 tumours, one also had a rare, apparently homozygous, sequence variant at codon 361. Because of the rarity of the combination of homozygous sequence variants, analysis for hemizygous deletion was pursued in the 15 samples and loss of heterozygosity was found in 11 tumours. Our data suggest that intragenic point mutations of GDNF or GFRα-1 are not a common aetiologic event in brain tumours. However, either deletion of GFRα-1 and/or nearby genes may contribute to the pathogenesis of these tumours
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