594 research outputs found
Expression of the myosin heavy chain IIB gene in porcine skeletal muscle: the role of the CArG-box promoter response element
Due to its similarity to humans, the pig is increasingly being considered as a good animal model for studying a range of human diseases. Despite their physiological similarities, differential expression of the myosin heavy chain (MyHC) IIB gene (MYH4) exists in the skeletal muscles of these species, which is associated with a different muscle phenotype. The expression of different MyHC isoforms is a critical determinant of the contractile and metabolic characteristics of the muscle fibre. We aimed to elucidate whether a genomic mechanism was responsible for the drastically different expression of MYH4 between pigs and humans, thus improving our understanding of the pig as a model for human skeletal muscle research. We utilized approximately 1 kb of the MYH4 promoter from a domestic pig and a human (which do and do not express MYH4, respectively) to elucidate the role of the promoter sequence in regulating the high expression of MYH4 in porcine skeletal muscle. We identified a 3 bp genomic difference within the proximal CArG and Ebox region of the MYH4 promoter of pigs and humans that dictates the differential activity of these promoters during myogenesis. Subtle species-specific genomic differences within the CArG-box region caused differential protein-DNA interactions at this site and is likely accountable for the differential MYH4 promoter activity between pigs and humans. We propose that the genomic differences identified herein explain the differential activity of the MYH4 promoter of pigs and humans, which may contribute to the differential expression patterns displayed in these otherwise physiologically similar mammals. Further, we report that both the pig and human MYH4 promoters can be induced by MyoD over- expression, but the capacity to activate the MYH4 promoter is largely influenced by the 3 bp difference located within the CArG-box region of the proximal MYH4 promoter
A questionnaire to collect unintended effects of transcranial magnetic stimulation: A consensus based approach
Transcranial magnetic stimulation (TMS) has been widely used in both clinical and research practice. However, TMS might induce unintended sensations and undesired effects as well as serious adverse effects. To date, no shared forms are available to report such unintended effects. This study aimed at developing a questionnaire enabling reporting of TMS unintended effects. A Delphi procedure was applied which allowed consensus among TMS experts. A steering committee nominated a number of experts to be involved in the Delphi procedure. Three rounds were conducted before reaching a consen-sus. Afterwards, the questionnaire was publicized on the International Federation of Clinical Neurophysiology website to collect further suggestions by the wider scientific community. A last Delphi round was then conducted to obtain consensus on the suggestions collected during the publiciza-tion and integrate them in the questionnaire. The procedure resulted in a questionnaire, that is the TMSens_Q, applicable in clinical and research settings. Routine use of the structured TMS questionnaire and standard reporting of unintended TMS effects will help to monitor the safety of TMS, particularly when applying new protocols. It will also improve the quality of data collection as well as the interpre-tation of experimental findings.(c) 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Detection of variable VHE gamma-ray emission from the extra-galactic gamma-ray binary LMC P3
Context. Recently, the high-energy (HE, 0.1-100 GeV) -ray emission
from the object LMC P3 in the Large Magellanic Cloud (LMC) has been discovered
to be modulated with a 10.3-day period, making it the first extra-galactic
-ray binary.
Aims. This work aims at the detection of very-high-energy (VHE, >100 GeV)
-ray emission and the search for modulation of the VHE signal with the
orbital period of the binary system.
Methods. LMC P3 has been observed with the High Energy Stereoscopic System
(H.E.S.S.); the acceptance-corrected exposure time is 100 h. The data set has
been folded with the known orbital period of the system in order to test for
variability of the emission. Energy spectra are obtained for the orbit-averaged
data set, and for the orbital phase bin around the VHE maximum.
Results. VHE -ray emission is detected with a statistical
significance of 6.4 . The data clearly show variability which is
phase-locked to the orbital period of the system. Periodicity cannot be deduced
from the H.E.S.S. data set alone. The orbit-averaged luminosity in the
TeV energy range is erg/s. A luminosity of erg/s is reached during 20% of the orbit. HE and VHE
-ray emissions are anti-correlated. LMC P3 is the most luminous
-ray binary known so far.Comment: 5 pages, 3 figures, 1 table, accepted for publication in A&
Characterizing the gamma-ray long-term variability of PKS 2155-304 with H.E.S.S. and Fermi-LAT
Studying the temporal variability of BL Lac objects at the highest energies
provides unique insights into the extreme physical processes occurring in
relativistic jets and in the vicinity of super-massive black holes. To this
end, the long-term variability of the BL Lac object PKS 2155-304 is analyzed in
the high (HE, 100 MeV 200 GeV)
gamma-ray domain. Over the course of ~9 yr of H.E.S.S observations the VHE
light curve in the quiescent state is consistent with a log-normal behavior.
The VHE variability in this state is well described by flicker noise
(power-spectral-density index {\ss}_VHE = 1.10 +0.10 -0.13) on time scales
larger than one day. An analysis of 5.5 yr of HE Fermi LAT data gives
consistent results ({\ss}_HE = 1.20 +0.21 -0.23, on time scales larger than 10
days) compatible with the VHE findings. The HE and VHE power spectral densities
show a scale invariance across the probed time ranges. A direct linear
correlation between the VHE and HE fluxes could neither be excluded nor firmly
established. These long-term-variability properties are discussed and compared
to the red noise behavior ({\ss} ~ 2) seen on shorter time scales during
VHE-flaring states. The difference in power spectral noise behavior at VHE
energies during quiescent and flaring states provides evidence that these
states are influenced by different physical processes, while the compatibility
of the HE and VHE long-term results is suggestive of a common physical link as
it might be introduced by an underlying jet-disk connection.Comment: 11 pages, 16 figure
Cortical disinhibition occurs in chronic neuropathic, but not in chronic nociceptive pain
<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the relationship between chronic neuropathic pain after incomplete peripheral nerve lesion, chronic nociceptive pain due to osteoarthritis, and the excitability of the motor cortex assessed by transcranial magnetic stimulation (TMS). Hence in 26 patients with neuropathic pain resulting from an isolated incomplete lesion of the median or ulnar nerve (neuralgia), 20 patients with painful osteoarthritis of the hand, and 14 healthy control subjects, the excitability of the motor cortex was tested using paired-pulse TMS to assess intracortical inhibition and facilitation. These excitability parameters were compared between groups, and the relationship between excitability parameters and clinical parameters was examined.</p> <p>Results</p> <p>We found a significant reduction of intracortical inhibition in the hemisphere contralateral to the lesioned nerve in the neuralgia patients. Intracortical inhibition in the ipsilateral hemisphere of neuralgia patients and in both hemispheres of osteoarthritis patients did not significantly differ from the control group. Disinhibition was significantly more pronounced in neuralgia patients with moderate/severe pain intensity than in patients with mild pain intensity, whereas the relative compound motor action potential as a parameter of nerve injury severity did not correlate with the amount of disinhibition.</p> <p>Conclusions</p> <p>Our results suggest a close relationship between motor cortex inhibition and chronic neuropathic pain in the neuralgia patients, which is independent from nerve injury severity. The lack of cortical disinhibition in patients with painful osteoarthritis points at differences in the pathophysiological processes of different chronic pain conditions with respect to the involvement of different brain circuitry.</p
Transcranial Direct Current Stimulation Improves Isometric Time to Exhaustion of the Knee Extensors
Transcranial direct current stimulation (tDCS) can increase cortical excitability of a targeted brain area, which may affect endurance exercise performance. However, optimal electrode placement for tDCS remains unclear. We tested the effect of two different tDCS electrode montages for improving exercise performance. Nine subjects underwent a control (CON), placebo (SHAM) and two different tDCS montage sessions in a randomized design. In one tDCS session, the anodal electrode was placed over the left motor cortex and the cathodal on contralateral forehead (HEAD), while for the other montage the anodal electrode was placed over the left motor cortex and cathodal electrode above the shoulder (SHOULDER). tDCS was delivered for 10min at 2.0mA, after which participants performed an isometric time to exhaustion (TTE) test of the right knee extensors. Peripheral and central neuromuscular parameters were assessed at baseline, after tDCS application and after TTE. Heart rate (HR), ratings of perceived exertion (RPE), and leg muscle exercise-induced muscle pain (PAIN) were monitored during the TTE. TTE was longer and RPE lower in the SHOULDER condition (P0.05). In all conditions maximal voluntary contraction (MVC) significantly decreased after the TTE (P<0.05) while motor-evoked potential area (MEP) increased after TTE (P<0.05). These findings demonstrate that SHOULDER montage is more effective than HEAD montage to improve endurance performance, likely through avoiding the negative effects of the cathode on excitability
Clinical risk stratification of paediatric renal transplant recipients using C1q and C3d fixing of de novo donor-specific antibodies
Introduction: We have previously shown that children who developed de novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) had greater decline in allograft function. We hypothesised that patients with complement-activating DSA would have poorer renal allograft outcomes. Methods: A total of 75 children developed DSA in the original study. The first positive DSA sample was subsequently tested for C1q and C3d fixing. The primary event was defined as 50% reduction from baseline estimated glomerular filtration rate and was analysed using the KaplanâMeier estimator. Results: Of 65 patients tested, 32 (49%) and 23 (35%) tested positive for C1q and C3d fixing, respectively. Of the 32 C1q-positive (c1q+) patients, 13 (41%) did not show concomitant C3d fixing. The mean fluorescence intensity values of the original immunoglobulin G DSA correlated poorly with complement-fixing positivity (C1q: adjusted R2 0.072; C3d: adjusted R2 0.11; p < 0.05). C1q+ antibodies were associated with acute tubulitis [0.75 ± 0.18 (C1q+) vs. 0.25 ± 0.08 (C1qâ) episodes per patient (mean ± standard error of the mean; p < 0.05] but not with worse long-term renal allograft dysfunction (median time to primary event 5.9 (C1q+) vs. 6.4 (C1qâ) years; hazard ratio (HR) 0.74; 95% confidence ratio (CI) 0.30â1.81; p = 0.58]. C3d-positive (C3d+) antibodies were associated with positive C4d histological staining [47% (C3d+) vs. 20% (C3dâ); p = 0.04] and with significantly worse long-term allograft dysfunction [median time to primary event: 5.6 (C3d+) vs. 6.5 (C3dâ) years; HR 0.38; 95% CI 0.15â0.97; p = 0.04]. Conclusion: Assessment of C3d fixing as part of prospective HLA monitoring can potentially aid stratification of patients at the highest risk of long-term renal allograft dysfunction
Detailed spectral and morphological analysis of the shell type SNR RCW 86
Aims: We aim for an understanding of the morphological and spectral
properties of the supernova remnant RCW~86 and for insights into the production
mechanism leading to the RCW~86 very high-energy gamma-ray emission. Methods:
We analyzed High Energy Spectroscopic System data that had increased
sensitivity compared to the observations presented in the RCW~86 H.E.S.S.
discovery publication. Studies of the morphological correlation between the
0.5-1~keV X-ray band, the 2-5~keV X-ray band, radio, and gamma-ray emissions
have been performed as well as broadband modeling of the spectral energy
distribution with two different emission models. Results:We present the first
conclusive evidence that the TeV gamma-ray emission region is shell-like based
on our morphological studies. The comparison with 2-5~keV X-ray data reveals a
correlation with the 0.4-50~TeV gamma-ray emission.The spectrum of RCW~86 is
best described by a power law with an exponential cutoff at TeV and a spectral index of ~. A static
leptonic one-zone model adequately describes the measured spectral energy
distribution of RCW~86, with the resultant total kinetic energy of the
electrons above 1 GeV being equivalent to 0.1\% of the initial kinetic
energy of a Type I a supernova explosion. When using a hadronic model, a
magnetic field of ~100G is needed to represent the measured data.
Although this is comparable to formerly published estimates, a standard
E spectrum for the proton distribution cannot describe the gamma-ray
data. Instead, a spectral index of ~1.7 would be required, which
implies that ~erg has been transferred into
high-energy protons with the effective density cm^-3. This
is about 10\% of the kinetic energy of a typical Type Ia supernova under the
assumption of a density of 1~cm^-3.Comment: accepted for publication by A&
The exceptionally powerful TeV gamma-ray emitters in the Large Magellanic Cloud
The Large Magellanic Cloud, a satellite galaxy of the Milky Way, has been
observed with the High Energy Stereoscopic System (H.E.S.S.) above an energy of
100 billion electron volts for a deep exposure of 210 hours. Three sources of
different types were detected: the pulsar wind nebula of the most energetic
pulsar known N 157B, the radio-loud supernova remnant N 132D and the largest
non-thermal X-ray shell - the superbubble 30 Dor C. The unique object SN 1987A
is, surprisingly, not detected, which constrains the theoretical framework of
particle acceleration in very young supernova remnants. These detections reveal
the most energetic tip of a gamma-ray source population in an external galaxy,
and provide via 30 Dor C the unambiguous detection of gamma-ray emission from a
superbubble.Comment: Published in Science Magazine (Jan. 23, 2015). This ArXiv version has
the supplementary online material incorporated as an appendix to the main
pape
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